Public Example BRCA
This document is not intended to support clinical reporting and must be strictly limited to academic research use only.
Cancer Type:
Invasive Breast Carcinoma
Putative functionally relevant variants: 3
| Gene | Gene Info | Alteration | Functional relevance evidence | Reported biomarker(s) |
|---|---|---|---|---|
|
ERBB2
|
OG
Oncogene
This gene acts (predominantly) as an oncogene, and thus activating alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
missense
p.Leu755Ser
exon 19/27
more
chr17:37880220 T/C (GRCh37/hg19)
Transcript: ENST00000269571 HGVSp: ENSP00000269571.4:p.Leu755Ser HGVSc: ENST00000269571.5:c.2264T>C Location: exon 19/27 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000406381 HGVSp: ENSP00000385185.2:p.Leu725Ser HGVSc: ENST00000406381.2:c.2174T>C Location: exon 21/29 Consequence: missense variant ──────────────────────── Transcript: ENST00000445658 HGVSp: ENSP00000404047.2:p.Leu479Ser HGVSc: ENST00000445658.2:c.1436T>C Location: exon 13/21 Consequence: missense variant ──────────────────────── Transcript: ENST00000540147 HGVSp: ENSP00000443562.1:p.Leu725Ser HGVSc: ENST00000540147.1:c.2174T>C Location: exon 19/27 Consequence: missense variant ──────────────────────── Transcript: ENST00000541774 HGVSp: ENSP00000446466.1:p.Leu740Ser HGVSc: ENST00000541774.1:c.2219T>C Location: exon 19/27 Consequence: missense variant ──────────────────────── Transcript: ENST00000578373 HGVSp: - HGVSc: ENST00000578373.1:c.*2054T>C Location: exon 19/27 Consequence: 3 prime UTR variant,NMD transcript variant ──────────────────────── Transcript: ENST00000578630 HGVSp: - HGVSc: ENST00000578630.1:n.873T>C Location: exon 5/5 Consequence: non coding transcript exon variant ──────────────────────── Transcript: ENST00000580074 HGVSp: ENSP00000463002.1:p.Leu124Ser HGVSc: ENST00000580074.1:c.371T>C Location: exon 4/6 Consequence: missense variant ──────────────────────── Transcript: ENST00000580969 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant ──────────────────────── Transcript: ENST00000582818 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000582963 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000583038 HGVSp: - HGVSc: ENST00000583038.1:n.3398T>C Location: exon 15/17 Consequence: non coding transcript exon variant ──────────────────────── Transcript: ENST00000584450 HGVSp: ENSP00000463714.1:p.Leu755Ser HGVSc: ENST00000584450.1:c.2264T>C Location: exon 19/26 Consequence: missense variant ──────────────────────── Transcript: ENST00000584601 HGVSp: ENSP00000462438.1:p.Leu725Ser HGVSc: ENST00000584601.1:c.2174T>C Location: exon 23/31 Consequence: missense variant ──────────────────────── Transcript: ENST00000584684 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000584888 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant |
Evidence A (curated):
>Oncogenic, Biomarker, OncoKB
ERBB2 p.Leu755Ser https://oncokb.org/#/gene/ERBB2/alteration/L755S Effect: Oncogenic, Biomarker The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. >Resistance, Sensitivity/Response, CIViC
ERBB2 p.Leu755Ser https://civicdb.org/links/variants/666 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Neratinib Disease: breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28679771 https://civicdb.org/links/variants/666 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Platinum Compound Disease: bladder carcinoma Evidence level: C - Case study Trust rating: 3/5 Source PMID: 25636205 https://civicdb.org/links/variants/39 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Neratinib Disease: breast cancer Evidence level: D - Preclinical Trust rating: 5/5 Source PMID: 23220880 https://civicdb.org/links/variants/39 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Lapatinib Disease: breast cancer Evidence level: D - Preclinical Trust rating: 5/5 Source PMID: 23220880
Inconclusive curation:
>Inconclusive/weaker evidence, ClinVar
ERBB2 p.Leu755Ser https://www.ncbi.nlm.nih.gov/clinvar/variation/376035 Effect: Likely pathogenic Allele origin: ERBB2 Review status: no assertion criteria provided |
Tier 1-Ready for use, 1 assertions
Tier 1 includes variants described as drug/prognostic biomarkers with ready-for-use clinical data for this cancer type
Please check the original assertions provided by each knowledgebase listed below >Reported sensitivity/response: Fulvestrant; Neratinib; Trastuzumab https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Neratinib,Trastuzumab,Fulvestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. Tier 2-Investigational, 2 assertions
Tier 2 includes variants described as drug/prognostic biomarkers according to investigational clinical data for this cancer type
Please check the original assertions provided by each knowledgebase listed below >Reported sensitivity/response: Neratinib https://civicdb.org/links/variants/666 Biomarker: ERBB2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Neratinib Disease: breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28679771 https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_3A Drug: Neratinib Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. Tier 3-Cancer repurposing, 10 assertions
Tier 3 includes variants described as drug/prognostic biomarkers for other cancer types (cancer type repurposing)
Please check the original assertions provided by each knowledgebase listed below >Reported sensitivity/response: Ado-Trastuzumab Emtansine; Docetaxel; Neratinib; Pertuzumab; Platinum Compound; Sevabertinib; Trastuzumab; Trastuzumab Deruxtecan; Zongertinib https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Zongertinib Disease: Non-Small Cell Lung Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_3A Drug: Sevabertinib Disease: Non-Small Cell Lung Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Ado-Trastuzumab Emtansine Disease: Non-Small Cell Lung Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Trastuzumab Deruxtecan Disease: Non-Small Cell Lung Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_3A Drug: Trastuzumab,Pertuzumab,Docetaxel Disease: Non-Small Cell Lung Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/ERBB2/alteration/L726F, L841V, L726I, T733I, L768S, L755A, Exon 20 in-frame insertions, L755P, L755S, L755W, D821N, D769H, D769Y, G776S, G776V, V777L, V777M, V794M, T798M, D808N, V773L, G815R, L866M, I767M, V842I, L869R Biomarker: ERBB2 L726F, L841V, L726I, T733I, L768S, L755A, Exon 20 in-frame insertions, L755P, L755S, L755W, D821N, D769H, D769Y, G776S, G776V, V777L, V777M, V794M, T798M, D808N, V773L, G815R, L866M, I767M, V842I, L869R Effect: drug Responsive Evidence level: LEVEL_1 Drug: Sevabertinib Disease: Non-Small Cell Lung Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/ERBB2/alteration/L726F, L841V, L726I, T733I, L768S, L755A, Exon 20 in-frame insertions, L755P, L755S, L755W, D821N, D769H, D769Y, G776S, G776V, V777L, V777M, V794M, T798M, D808N, V773L, G815R, L866M, I767M, V842I, L869R Biomarker: ERBB2 L726F, L841V, L726I, T733I, L768S, L755A, Exon 20 in-frame insertions, L755P, L755S, L755W, D821N, D769H, D769Y, G776S, G776V, V777L, V777M, V794M, T798M, D808N, V773L, G815R, L866M, I767M, V842I, L869R Effect: drug Responsive Evidence level: LEVEL_1 Drug: Zongertinib Disease: Non-Small Cell Lung Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_3A Drug: Neratinib Disease: Non-Small Cell Lung Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://civicdb.org/links/variants/666 Biomarker: ERBB2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Platinum Compound Disease: bladder carcinoma Evidence level: C - Case study Trust rating: 3/5 Source PMID: 25636205 https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Neratinib Disease: Cervical Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. Tier 4-Hypothetical, 2 assertions
Tier 4 includes variants described as drug/prognostic biomarkers according to preclinical data
Please check the original assertions provided by each knowledgebase listed below >Reported sensitivity/response: Lapatinib; Neratinib https://civicdb.org/links/variants/39 Biomarker: ERBB2 L755S Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Neratinib Disease: breast cancer Evidence level: D - Preclinical Trust rating: 5/5 Source PMID: 23220880 https://civicdb.org/links/variants/39 Biomarker: ERBB2 L755S Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Lapatinib Disease: breast cancer Evidence level: D - Preclinical Trust rating: 5/5 Source PMID: 23220880 |
|
ESR1
|
OG
Oncogene
This gene acts (predominantly) as an oncogene, and thus activating alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
missense
p.Tyr537Ser
exon 8/8
more
chr6:152419923 A/C (GRCh37/hg19)
Transcript: ENST00000206249 HGVSp: ENSP00000206249.3:p.Tyr537Ser HGVSc: ENST00000206249.3:c.1610A>C Location: exon 8/8 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000338799 HGVSp: ENSP00000342630.5:p.Tyr537Ser HGVSc: ENST00000338799.5:c.1610A>C Location: exon 9/9 Consequence: missense variant ──────────────────────── Transcript: ENST00000406599 HGVSp: ENSP00000384064.1:p.Tyr276Ser HGVSc: ENST00000406599.1:c.827A>C Location: exon 4/4 Consequence: missense variant ──────────────────────── Transcript: ENST00000427531 HGVSp: - HGVSc: ENST00000427531.2:c.851-26478A>C Location: intron 6/6 Consequence: intron variant ──────────────────────── Transcript: ENST00000440973 HGVSp: ENSP00000405330.1:p.Tyr537Ser HGVSc: ENST00000440973.1:c.1610A>C Location: exon 10/10 Consequence: missense variant ──────────────────────── Transcript: ENST00000443427 HGVSp: ENSP00000387500.1:p.Tyr537Ser HGVSc: ENST00000443427.1:c.1610A>C Location: exon 9/9 Consequence: missense variant ──────────────────────── Transcript: ENST00000456483 HGVSp: ENSP00000415934.2:p.Tyr425Ser HGVSc: ENST00000456483.2:c.1274A>C Location: exon 8/8 Consequence: missense variant |
Evidence A (curated):
>Oncogenic, Biomarker, OncoKB
ESR1 p.Tyr537Ser https://oncokb.org/#/gene/ESR1/alteration/Y537S Effect: Oncogenic, Biomarker The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. >Resistance, Sensitivity/Response, CIViC
ESR1 p.Tyr537Ser https://civicdb.org/links/variants/3910 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Elacestrant Disease: breast cancer Evidence level: A - Guideline Trust rating: 4/5 Source PMID: 35584336 https://civicdb.org/links/variants/50 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Tamoxifen,Fulvestrant Disease: breast cancer Evidence level: D - Preclinical Trust rating: 5/5 Source PMID: 24185510 https://civicdb.org/links/variants/50 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Hormone Therapy Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 24185512 |
Tier 1-Ready for use, 3 assertions
Tier 1 includes variants described as drug/prognostic biomarkers with ready-for-use clinical data for this cancer type
Please check the original assertions provided by each knowledgebase listed below >Reported sensitivity/response: Elacestrant; Imlunestrant https://civicdb.org/links/variants/3910 Biomarker: ESR1 MUTATION Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Elacestrant Disease: breast cancer Evidence level: A - Guideline Trust rating: 4/5 Source PMID: 35584336 https://oncokb.org/#/gene/ESR1/alteration/S463F, D538, E380, Y537, L536, L469V, S463P, V422del Biomarker: ESR1 S463F, D538, E380, Y537, L536, L469V, S463P, V422del Effect: drug Responsive Evidence level: LEVEL_1 Drug: Imlunestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/ESR1/alteration/G442R, F461V, D538, E380, Y537, L536, L469V, S463P Biomarker: ESR1 G442R, F461V, D538, E380, Y537, L536, L469V, S463P Effect: drug Responsive Evidence level: LEVEL_1 Drug: Elacestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. Tier 2-Investigational, 2 assertions
Tier 2 includes variants described as drug/prognostic biomarkers according to investigational clinical data for this cancer type
Please check the original assertions provided by each knowledgebase listed below >Reported sensitivity/response: Fulvestrant https://oncokb.org/#/gene/ESR1/alteration/Oncogenic Mutations (excluding Fusions) Biomarker: ESR1 Oncogenic Mutations (excluding Fusions) Effect: drug Responsive Evidence level: LEVEL_3A Drug: Fulvestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/ESR1/alteration/Oncogenic Mutations (excluding Fusions) Biomarker: ESR1 Oncogenic Mutations (excluding Fusions) Effect: drug Responsive Evidence level: LEVEL_3A Drug: Fulvestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. Tier 4-Hypothetical, 2 assertions
Tier 4 includes variants described as drug/prognostic biomarkers according to preclinical data
Please check the original assertions provided by each knowledgebase listed below >Reported sensitivity/response: Fulvestrant; Hormone Therapy; Tamoxifen https://civicdb.org/links/variants/50 Biomarker: ESR1 Y537S Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Tamoxifen,Fulvestrant Disease: breast cancer Evidence level: D - Preclinical Trust rating: 5/5 Source PMID: 24185510 https://civicdb.org/links/variants/50 Biomarker: ESR1 Y537S Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Hormone Therapy Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 24185512 |
|
PIK3CA
|
OG
Oncogene
This gene acts (predominantly) as an oncogene, and thus activating alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
missense
p.Glu545Lys
exon 10/21
more
chr3:178936091 G/A (GRCh37/hg19)
Transcript: ENST00000263967 HGVSp: ENSP00000263967.3:p.Glu545Lys HGVSc: ENST00000263967.3:c.1633G>A Location: exon 10/21 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000462255 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant |
Evidence A (curated):
>Pathogenic/Likely pathogenic, ClinVar
PIK3CA p.Glu545Lys https://www.ncbi.nlm.nih.gov/clinvar/variation/13655 Effect: Pathogenic/Likely pathogenic Allele origin: PIK3CA Review status: criteria provided, multiple submitters, no conflicts >Oncogenic, Biomarker, OncoKB
PIK3CA p.Glu545Lys https://oncokb.org/#/gene/PIK3CA/alteration/E545K Effect: Oncogenic, Biomarker The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. >Poor Outcome, Resistance, Sensitivity/Response, CIViC
PIK3CA p.Glu545Lys https://civicdb.org/links/variants/106 Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Poor Outcome Drug: n/a Disease: breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 17947469 https://civicdb.org/links/variants/311 Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Better Outcome Drug: - Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 17575221 https://civicdb.org/links/variants/311 Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Better Outcome Drug: - Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19671852 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Fulvestrant,Alpelisib Disease: breast cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 31091374 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Copanlisib Disease: cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 35133871 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28489509 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21594665 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Everolimus Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 27091708 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Lapatinib,Capecitabine Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 26920887 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21594665 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Panitumumab,Cetuximab Disease: colorectal cancer Evidence level: C - Case study Trust rating: 3/5 Source PMID: 19223544 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Aspirin Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 23094721 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Sulindac,Celecoxib,Aspirin Disease: head and neck squamous cell carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 30683736 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Anti-EGFR Monoclonal Antibody Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 23435830 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Erlotinib,Gefitinib Disease: lung non-small cell carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21258250 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Panitumumab,Cetuximab Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19223544 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Cetuximab Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19603024 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Alpelisib Disease: cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 24608574 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 22294718 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Pictilisib Disease: her2-receptor positive breast cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 20453058 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Pictilisib,Akt Inhibitor MK2206 Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 23888070 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab,Lapatinib Disease: her2-receptor positive breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 19010894 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Phosphatidylinositide 3-Kinase Inhibitor,Ribociclib Disease: breast cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 25002028 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: MTOR Kinase Inhibitor PP242,Everolimus Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 21358673 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Palbociclib,Phosphatidylinositide 3-Kinase Inhibitor Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 25002028
Inconclusive curation:
>Population AF<1%, gnomAD/1000G
PIK3CA p.Glu545Lys This variant is observed across population databases with max AF< 1% (8.879e-06), which is the threshold used to assume that the variant should be neutral gnomAD combined population: 4.032e-06 gnomAD African/African American: 0 gnomAD Ashkenazi Jewish: 0 gnomAD East Asian: 0 gnomAD European (Finnish): 0 gnomAD European (non-Finnish): 8.879e-06 gnomAD South Asian: 0 gnomAD Other: 0 1000G European: - 1000G African: - 1000G American: - 1000G East Asian: - 1000G South Asian: - >Inconclusive/weaker evidence, ClinVar
PIK3CA p.Glu545Lys https://www.ncbi.nlm.nih.gov/clinvar/variation/2672088 Effect: Pathogenic Allele origin: PIK3CA Review status: criteria provided, single submitter |
Others - Prognostic, 3 assertions
Alterations reported to be prognostic biomarkers
Please check the original assertions provided by each knowledgebase listed below https://civicdb.org/links/variants/106 Biomarker: PIK3CA Exon 10 Mutation Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Poor Outcome Drug: n/a Disease: breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 17947469 https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Better Outcome Drug: - Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 17575221 https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Better Outcome Drug: - Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19671852 Tier 1-Ready for use, 6 assertions
Tier 1 includes variants described as drug/prognostic biomarkers with ready-for-use clinical data for this cancer type
Please check the original assertions provided by each knowledgebase listed below >Reported sensitivity/response: Alpelisib; Capivasertib; Fulvestrant; Inavolisib; Palbociclib https://oncokb.org/#/gene/PIK3CA/alteration/H1047L, H1047R, E545A, H1047Y, Q546R, C420R, E545K, E542K, E545D, E545G, Q546E Biomarker: PIK3CA H1047L, H1047R, E545A, H1047Y, Q546R, C420R, E545K, E542K, E545D, E545G, Q546E Effect: drug Responsive Evidence level: LEVEL_1 Drug: Capivasertib,Fulvestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/PIK3CA/alteration/Oncogenic Mutations (excluding C420R, E542K, E545A, E545D, E545G, E545K, Q546E, Q546R, H1047L, H1047R and H1047Y) Biomarker: PIK3CA Oncogenic Mutations (excluding C420R, E542K, E545A, E545D, E545G, E545K, Q546E, Q546R, H1047L, H1047R and H1047Y) Effect: drug Responsive Evidence level: LEVEL_2 Drug: Alpelisib,Fulvestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/PIK3CA/alteration/Oncogenic Mutations (excluding C420R, E542K, E545A, E545D, E545G, E545K, Q546E, Q546R, H1047L, H1047R, H1047Y, R88Q, N345K, E545Q, Q546K, Q546P, M1043V, M1043I and G1049R) Biomarker: PIK3CA Oncogenic Mutations (excluding C420R, E542K, E545A, E545D, E545G, E545K, Q546E, Q546R, H1047L, H1047R, H1047Y, R88Q, N345K, E545Q, Q546K, Q546P, M1043V, M1043I and G1049R) Effect: drug Responsive Evidence level: LEVEL_2 Drug: Capivasertib,Fulvestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/PIK3CA/alteration/H1047L, H1047R, E545A, H1047Y, Q546R, C420R, E545K, E542K, E545D, E545G, Q546E Biomarker: PIK3CA H1047L, H1047R, E545A, H1047Y, Q546R, C420R, E545K, E542K, E545D, E545G, Q546E Effect: drug Responsive Evidence level: LEVEL_1 Drug: Alpelisib,Fulvestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/PIK3CA/alteration/Oncogenic Mutations Biomarker: PIK3CA Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Inavolisib,Palbociclib,Fulvestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Fulvestrant,Alpelisib Disease: breast cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 31091374 Tier 2-Investig. (basket match), 2 assertions
Tier 2 includes variants described as drug/prognostic biomarkers according to investigational clinical data for this cancer type
Please check the original assertions provided by each knowledgebase listed below >Reported sensitivity/response: Capivasertib; Copanlisib https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Copanlisib Disease: cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 35133871 https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28489509 Tier 2-Investigational, 4 assertions
Tier 2 includes variants described as drug/prognostic biomarkers according to investigational clinical data for this cancer type
Please check the original assertions provided by each knowledgebase listed below >Reported sensitivity/response: Capecitabine; Everolimus; Lapatinib; Trastuzumab https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21594665 https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Everolimus Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 27091708 https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Lapatinib,Capecitabine Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 26920887 https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21594665 Tier 3-Cancer repurposing, 7 assertions
Tier 3 includes variants described as drug/prognostic biomarkers for other cancer types (cancer type repurposing)
Please check the original assertions provided by each knowledgebase listed below >Reported sensitivity/response: Anti-EGFR Monoclonal Antibody; Aspirin; Celecoxib; Cetuximab; Erlotinib; Gefitinib; Panitumumab; Sulindac https://civicdb.org/links/variants/104 Biomarker: PIK3CA E545K Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Panitumumab,Cetuximab Disease: colorectal cancer Evidence level: C - Case study Trust rating: 3/5 Source PMID: 19223544 https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Aspirin Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 23094721 https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Sulindac,Celecoxib,Aspirin Disease: head and neck squamous cell carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 30683736 https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Anti-EGFR Monoclonal Antibody Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 23435830 https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Erlotinib,Gefitinib Disease: lung non-small cell carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21258250 https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Panitumumab,Cetuximab Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19223544 https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Cetuximab Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19603024 Tier 4-Hypothet. (basket match), 3 assertions
Tier 4 includes variants described as drug/prognostic biomarkers according to preclinical data
Please check the original assertions provided by each knowledgebase listed below >Reported sensitivity/response: Alpelisib; Capivasertib; RLY-2608 https://oncokb.org/#/gene/PIK3CA/alteration/Oncogenic Mutations Biomarker: PIK3CA Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_4 Drug: RLY-2608 Disease: SOLID The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Alpelisib Disease: cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 24608574 https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 22294718 Tier 4-Hypothetical, 7 assertions
Tier 4 includes variants described as drug/prognostic biomarkers according to preclinical data
Please check the original assertions provided by each knowledgebase listed below >Reported sensitivity/response: Akt Inhibitor MK2206; Everolimus; Fulvestrant; Lapatinib; MTOR Kinase Inhibitor PP242; Palbociclib; Phosphatidylinositide 3-Kinase Inhibitor; Pictilisib; RLY-2608; Ribociclib; Trastuzumab https://civicdb.org/links/variants/104 Biomarker: PIK3CA E545K Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Pictilisib Disease: her2-receptor positive breast cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 20453058 https://civicdb.org/links/variants/104 Biomarker: PIK3CA E545K Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Pictilisib,Akt Inhibitor MK2206 Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 23888070 https://civicdb.org/links/variants/104 Biomarker: PIK3CA E545K Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab,Lapatinib Disease: her2-receptor positive breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 19010894 https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Phosphatidylinositide 3-Kinase Inhibitor,Ribociclib Disease: breast cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 25002028 https://oncokb.org/#/gene/PIK3CA/alteration/Oncogenic Mutations Biomarker: PIK3CA Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_4 Drug: RLY-2608,Fulvestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: MTOR Kinase Inhibitor PP242,Everolimus Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 21358673 https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Palbociclib,Phosphatidylinositide 3-Kinase Inhibitor Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 25002028 |
Variants of unknown/contradictory functional significance: 1
| Gene | Gene Info | Alteration | Functional relevance evidence | Reported biomarker(s) |
|---|---|---|---|---|
|
CBFB
|
TS
Tumor Suppressor
This gene acts (predominantly) as a tumor suppressor, and thus loss-of-function (or dominant-negative) alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
missense
p.Asp128Val
exon 4/6
more
chr16:67100685 A/T (GRCh37/hg19)
Transcript: ENST00000290858 HGVSp: ENSP00000290858.6:p.Asp128Val HGVSc: ENST00000290858.6:c.383A>T Location: exon 4/6 Consequence: missense variant ──────────────────────── Transcript: ENST00000412916 HGVSp: ENSP00000415151.2:p.Asp128Val HGVSc: ENST00000412916.2:c.383A>T Location: exon 4/6 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000561924 HGVSp: ENSP00000462273.1:p.Asp28Val HGVSc: ENST00000561924.2:c.83A>T Location: exon 4/6 Consequence: missense variant ──────────────────────── Transcript: ENST00000563939 HGVSp: ENSP00000462148.1:p.Asp28Val HGVSc: ENST00000563939.2:c.83A>T Location: exon 3/4 Consequence: missense variant ──────────────────────── Transcript: ENST00000564034 HGVSp: ENSP00000456637.1:p.Asp89Val HGVSc: ENST00000564034.1:c.266A>T Location: exon 3/3 Consequence: missense variant ──────────────────────── Transcript: ENST00000565389 HGVSp: - HGVSc: ENST00000565389.1:c.113-31928A>T Location: intron 2/2 Consequence: intron variant ──────────────────────── Transcript: ENST00000567947 HGVSp: - HGVSc: ENST00000567947.1:n.430A>T Location: exon 2/2 Consequence: non coding transcript exon variant |
Inconclusive curation:
>No conclusive criteria, more
CBFB p.Asp128Val No conclusive effect for this variant is reported by the knowledgebases employed here. No biological bona fide assumption or bioinformatic prediction (see PMID: 35221333) applies and/or is conclusive to classify the variant. On detail for this variant, no |
Not contemplated
Potential match with cancer biomarkers is only contemplated for variants that are classified as functionally relevant.
|
Tier 1 - Ready for use biomarkers: 3
| Gene | Gene Info | Alteration | Functional relevance evidence | Biomarker |
|---|---|---|---|---|
|
ERBB2
|
OG
Oncogene
This gene acts (predominantly) as an oncogene, and thus activating alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
missense
p.Leu755Ser
exon 19/27
more
chr17:37880220 T/C (GRCh37/hg19)
Transcript: ENST00000269571 HGVSp: ENSP00000269571.4:p.Leu755Ser HGVSc: ENST00000269571.5:c.2264T>C Location: exon 19/27 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000406381 HGVSp: ENSP00000385185.2:p.Leu725Ser HGVSc: ENST00000406381.2:c.2174T>C Location: exon 21/29 Consequence: missense variant ──────────────────────── Transcript: ENST00000445658 HGVSp: ENSP00000404047.2:p.Leu479Ser HGVSc: ENST00000445658.2:c.1436T>C Location: exon 13/21 Consequence: missense variant ──────────────────────── Transcript: ENST00000540147 HGVSp: ENSP00000443562.1:p.Leu725Ser HGVSc: ENST00000540147.1:c.2174T>C Location: exon 19/27 Consequence: missense variant ──────────────────────── Transcript: ENST00000541774 HGVSp: ENSP00000446466.1:p.Leu740Ser HGVSc: ENST00000541774.1:c.2219T>C Location: exon 19/27 Consequence: missense variant ──────────────────────── Transcript: ENST00000578373 HGVSp: - HGVSc: ENST00000578373.1:c.*2054T>C Location: exon 19/27 Consequence: 3 prime UTR variant,NMD transcript variant ──────────────────────── Transcript: ENST00000578630 HGVSp: - HGVSc: ENST00000578630.1:n.873T>C Location: exon 5/5 Consequence: non coding transcript exon variant ──────────────────────── Transcript: ENST00000580074 HGVSp: ENSP00000463002.1:p.Leu124Ser HGVSc: ENST00000580074.1:c.371T>C Location: exon 4/6 Consequence: missense variant ──────────────────────── Transcript: ENST00000580969 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant ──────────────────────── Transcript: ENST00000582818 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000582963 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000583038 HGVSp: - HGVSc: ENST00000583038.1:n.3398T>C Location: exon 15/17 Consequence: non coding transcript exon variant ──────────────────────── Transcript: ENST00000584450 HGVSp: ENSP00000463714.1:p.Leu755Ser HGVSc: ENST00000584450.1:c.2264T>C Location: exon 19/26 Consequence: missense variant ──────────────────────── Transcript: ENST00000584601 HGVSp: ENSP00000462438.1:p.Leu725Ser HGVSc: ENST00000584601.1:c.2174T>C Location: exon 23/31 Consequence: missense variant ──────────────────────── Transcript: ENST00000584684 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000584888 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant |
Evidence A (curated):
>Oncogenic, Biomarker, OncoKB
ERBB2 p.Leu755Ser https://oncokb.org/#/gene/ERBB2/alteration/L755S Effect: Oncogenic, Biomarker The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. >Resistance, Sensitivity/Response, CIViC
ERBB2 p.Leu755Ser https://civicdb.org/links/variants/666 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Neratinib Disease: breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28679771 https://civicdb.org/links/variants/666 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Platinum Compound Disease: bladder carcinoma Evidence level: C - Case study Trust rating: 3/5 Source PMID: 25636205 https://civicdb.org/links/variants/39 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Neratinib Disease: breast cancer Evidence level: D - Preclinical Trust rating: 5/5 Source PMID: 23220880 https://civicdb.org/links/variants/39 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Lapatinib Disease: breast cancer Evidence level: D - Preclinical Trust rating: 5/5 Source PMID: 23220880
Inconclusive curation:
>Inconclusive/weaker evidence, ClinVar
ERBB2 p.Leu755Ser https://www.ncbi.nlm.nih.gov/clinvar/variation/376035 Effect: Likely pathogenic Allele origin: ERBB2 Review status: no assertion criteria provided |
Sensitivity/Response
> Neratinib; Trastuzumab; Fulvestrant (OncoKB
ERBB2 p.Leu755Ser Drug: Neratinib; Trastuzumab; Fulvestrant https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Neratinib;Trastuzumab;Fulvestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. |
|
PIK3CA
|
OG
Oncogene
This gene acts (predominantly) as an oncogene, and thus activating alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
missense
p.Glu545Lys
exon 10/21
more
chr3:178936091 G/A (GRCh37/hg19)
Transcript: ENST00000263967 HGVSp: ENSP00000263967.3:p.Glu545Lys HGVSc: ENST00000263967.3:c.1633G>A Location: exon 10/21 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000462255 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant |
Evidence A (curated):
>Pathogenic/Likely pathogenic, ClinVar
PIK3CA p.Glu545Lys https://www.ncbi.nlm.nih.gov/clinvar/variation/13655 Effect: Pathogenic/Likely pathogenic Allele origin: PIK3CA Review status: criteria provided, multiple submitters, no conflicts >Oncogenic, Biomarker, OncoKB
PIK3CA p.Glu545Lys https://oncokb.org/#/gene/PIK3CA/alteration/E545K Effect: Oncogenic, Biomarker The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. >Poor Outcome, Resistance, Sensitivity/Response, CIViC
PIK3CA p.Glu545Lys https://civicdb.org/links/variants/106 Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Poor Outcome Drug: n/a Disease: breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 17947469 https://civicdb.org/links/variants/311 Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Better Outcome Drug: - Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 17575221 https://civicdb.org/links/variants/311 Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Better Outcome Drug: - Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19671852 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Fulvestrant,Alpelisib Disease: breast cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 31091374 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Copanlisib Disease: cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 35133871 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28489509 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21594665 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Everolimus Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 27091708 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Lapatinib,Capecitabine Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 26920887 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21594665 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Panitumumab,Cetuximab Disease: colorectal cancer Evidence level: C - Case study Trust rating: 3/5 Source PMID: 19223544 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Aspirin Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 23094721 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Sulindac,Celecoxib,Aspirin Disease: head and neck squamous cell carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 30683736 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Anti-EGFR Monoclonal Antibody Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 23435830 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Erlotinib,Gefitinib Disease: lung non-small cell carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21258250 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Panitumumab,Cetuximab Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19223544 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Cetuximab Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19603024 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Alpelisib Disease: cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 24608574 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 22294718 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Pictilisib Disease: her2-receptor positive breast cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 20453058 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Pictilisib,Akt Inhibitor MK2206 Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 23888070 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab,Lapatinib Disease: her2-receptor positive breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 19010894 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Phosphatidylinositide 3-Kinase Inhibitor,Ribociclib Disease: breast cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 25002028 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: MTOR Kinase Inhibitor PP242,Everolimus Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 21358673 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Palbociclib,Phosphatidylinositide 3-Kinase Inhibitor Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 25002028
Inconclusive curation:
>Population AF<1%, gnomAD/1000G
PIK3CA p.Glu545Lys This variant is observed across population databases with max AF< 1% (8.879e-06), which is the threshold used to assume that the variant should be neutral gnomAD combined population: 4.032e-06 gnomAD African/African American: 0 gnomAD Ashkenazi Jewish: 0 gnomAD East Asian: 0 gnomAD European (Finnish): 0 gnomAD European (non-Finnish): 8.879e-06 gnomAD South Asian: 0 gnomAD Other: 0 1000G European: - 1000G African: - 1000G American: - 1000G East Asian: - 1000G South Asian: - >Inconclusive/weaker evidence, ClinVar
PIK3CA p.Glu545Lys https://www.ncbi.nlm.nih.gov/clinvar/variation/2672088 Effect: Pathogenic Allele origin: PIK3CA Review status: criteria provided, single submitter |
Sensitivity/Response
> Alpelisib; Fulvestrant (OncoKB
PIK3CA p.Glu545Lys Drug: Alpelisib; Fulvestrant 2 assertions found: https://oncokb.org/#/gene/PIK3CA/alteration/Oncogenic Mutations (excluding C420R, E542K, E545A, E545D, E545G, E545K, Q546E, Q546R, H1047L, H1047R and H1047Y) Biomarker: PIK3CA Oncogenic Mutations (excluding C420R, E542K, E545A, E545D, E545G, E545K, Q546E, Q546R, H1047L, H1047R and H1047Y) Effect: drug Responsive Evidence level: LEVEL_2 Drug: Alpelisib;Fulvestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/PIK3CA/alteration/H1047L, H1047R, E545A, H1047Y, Q546R, C420R, E545K, E542K, E545D, E545G, Q546E Biomarker: PIK3CA H1047L, H1047R, E545A, H1047Y, Q546R, C420R, E545K, E542K, E545D, E545G, Q546E Effect: drug Responsive Evidence level: LEVEL_1 Drug: Alpelisib;Fulvestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Capivasertib; Fulvestrant (OncoKB
PIK3CA p.Glu545Lys Drug: Capivasertib; Fulvestrant 2 assertions found: https://oncokb.org/#/gene/PIK3CA/alteration/H1047L, H1047R, E545A, H1047Y, Q546R, C420R, E545K, E542K, E545D, E545G, Q546E Biomarker: PIK3CA H1047L, H1047R, E545A, H1047Y, Q546R, C420R, E545K, E542K, E545D, E545G, Q546E Effect: drug Responsive Evidence level: LEVEL_1 Drug: Capivasertib;Fulvestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/PIK3CA/alteration/Oncogenic Mutations (excluding C420R, E542K, E545A, E545D, E545G, E545K, Q546E, Q546R, H1047L, H1047R, H1047Y, R88Q, N345K, E545Q, Q546K, Q546P, M1043V, M1043I and G1049R) Biomarker: PIK3CA Oncogenic Mutations (excluding C420R, E542K, E545A, E545D, E545G, E545K, Q546E, Q546R, H1047L, H1047R, H1047Y, R88Q, N345K, E545Q, Q546K, Q546P, M1043V, M1043I and G1049R) Effect: drug Responsive Evidence level: LEVEL_2 Drug: Capivasertib;Fulvestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Fulvestrant;Alpelisib (CIViC
PIK3CA p.Glu545Lys Drug: Fulvestrant;Alpelisib https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Fulvestrant,Alpelisib Disease: breast cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 31091374 > Inavolisib; Palbociclib; Fulvestrant (OncoKB
PIK3CA p.Glu545Lys Drug: Inavolisib; Palbociclib; Fulvestrant https://oncokb.org/#/gene/PIK3CA/alteration/Oncogenic Mutations Biomarker: PIK3CA Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Inavolisib;Palbociclib;Fulvestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. |
|
ESR1
|
OG
Oncogene
This gene acts (predominantly) as an oncogene, and thus activating alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
missense
p.Tyr537Ser
exon 8/8
more
chr6:152419923 A/C (GRCh37/hg19)
Transcript: ENST00000206249 HGVSp: ENSP00000206249.3:p.Tyr537Ser HGVSc: ENST00000206249.3:c.1610A>C Location: exon 8/8 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000338799 HGVSp: ENSP00000342630.5:p.Tyr537Ser HGVSc: ENST00000338799.5:c.1610A>C Location: exon 9/9 Consequence: missense variant ──────────────────────── Transcript: ENST00000406599 HGVSp: ENSP00000384064.1:p.Tyr276Ser HGVSc: ENST00000406599.1:c.827A>C Location: exon 4/4 Consequence: missense variant ──────────────────────── Transcript: ENST00000427531 HGVSp: - HGVSc: ENST00000427531.2:c.851-26478A>C Location: intron 6/6 Consequence: intron variant ──────────────────────── Transcript: ENST00000440973 HGVSp: ENSP00000405330.1:p.Tyr537Ser HGVSc: ENST00000440973.1:c.1610A>C Location: exon 10/10 Consequence: missense variant ──────────────────────── Transcript: ENST00000443427 HGVSp: ENSP00000387500.1:p.Tyr537Ser HGVSc: ENST00000443427.1:c.1610A>C Location: exon 9/9 Consequence: missense variant ──────────────────────── Transcript: ENST00000456483 HGVSp: ENSP00000415934.2:p.Tyr425Ser HGVSc: ENST00000456483.2:c.1274A>C Location: exon 8/8 Consequence: missense variant |
Evidence A (curated):
>Oncogenic, Biomarker, OncoKB
ESR1 p.Tyr537Ser https://oncokb.org/#/gene/ESR1/alteration/Y537S Effect: Oncogenic, Biomarker The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. >Resistance, Sensitivity/Response, CIViC
ESR1 p.Tyr537Ser https://civicdb.org/links/variants/3910 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Elacestrant Disease: breast cancer Evidence level: A - Guideline Trust rating: 4/5 Source PMID: 35584336 https://civicdb.org/links/variants/50 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Tamoxifen,Fulvestrant Disease: breast cancer Evidence level: D - Preclinical Trust rating: 5/5 Source PMID: 24185510 https://civicdb.org/links/variants/50 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Hormone Therapy Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 24185512 |
Sensitivity/Response
> Elacestrant (CIViC; OncoKB
ESR1 p.Tyr537Ser Drug: Elacestrant 2 assertions found: https://civicdb.org/links/variants/3910 Biomarker: ESR1 MUTATION Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Elacestrant Disease: breast cancer Evidence level: A - Guideline Trust rating: 4/5 Source PMID: 35584336 ──────────────────────── https://oncokb.org/#/gene/ESR1/alteration/G442R, F461V, D538, E380, Y537, L536, L469V, S463P Biomarker: ESR1 G442R, F461V, D538, E380, Y537, L536, L469V, S463P Effect: drug Responsive Evidence level: LEVEL_1 Drug: Elacestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Imlunestrant (OncoKB
ESR1 p.Tyr537Ser Drug: Imlunestrant https://oncokb.org/#/gene/ESR1/alteration/S463F, D538, E380, Y537, L536, L469V, S463P, V422del Biomarker: ESR1 S463F, D538, E380, Y537, L536, L469V, S463P, V422del Effect: drug Responsive Evidence level: LEVEL_1 Drug: Imlunestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. |
Special - Other biomarkers of clinical interest: 1
| Gene | Gene Info | Alteration | Functional relevance evidence | Biomarker |
|---|---|---|---|---|
|
PIK3CA
|
OG
Oncogene
This gene acts (predominantly) as an oncogene, and thus activating alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
missense
p.Glu545Lys
exon 10/21
more
chr3:178936091 G/A (GRCh37/hg19)
Transcript: ENST00000263967 HGVSp: ENSP00000263967.3:p.Glu545Lys HGVSc: ENST00000263967.3:c.1633G>A Location: exon 10/21 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000462255 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant |
Evidence A (curated):
>Pathogenic/Likely pathogenic, ClinVar
PIK3CA p.Glu545Lys https://www.ncbi.nlm.nih.gov/clinvar/variation/13655 Effect: Pathogenic/Likely pathogenic Allele origin: PIK3CA Review status: criteria provided, multiple submitters, no conflicts >Oncogenic, Biomarker, OncoKB
PIK3CA p.Glu545Lys https://oncokb.org/#/gene/PIK3CA/alteration/E545K Effect: Oncogenic, Biomarker The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. >Poor Outcome, Resistance, Sensitivity/Response, CIViC
PIK3CA p.Glu545Lys https://civicdb.org/links/variants/106 Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Poor Outcome Drug: n/a Disease: breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 17947469 https://civicdb.org/links/variants/311 Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Better Outcome Drug: - Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 17575221 https://civicdb.org/links/variants/311 Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Better Outcome Drug: - Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19671852 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Fulvestrant,Alpelisib Disease: breast cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 31091374 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Copanlisib Disease: cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 35133871 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28489509 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21594665 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Everolimus Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 27091708 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Lapatinib,Capecitabine Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 26920887 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21594665 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Panitumumab,Cetuximab Disease: colorectal cancer Evidence level: C - Case study Trust rating: 3/5 Source PMID: 19223544 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Aspirin Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 23094721 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Sulindac,Celecoxib,Aspirin Disease: head and neck squamous cell carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 30683736 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Anti-EGFR Monoclonal Antibody Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 23435830 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Erlotinib,Gefitinib Disease: lung non-small cell carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21258250 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Panitumumab,Cetuximab Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19223544 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Cetuximab Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19603024 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Alpelisib Disease: cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 24608574 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 22294718 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Pictilisib Disease: her2-receptor positive breast cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 20453058 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Pictilisib,Akt Inhibitor MK2206 Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 23888070 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab,Lapatinib Disease: her2-receptor positive breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 19010894 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Phosphatidylinositide 3-Kinase Inhibitor,Ribociclib Disease: breast cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 25002028 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: MTOR Kinase Inhibitor PP242,Everolimus Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 21358673 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Palbociclib,Phosphatidylinositide 3-Kinase Inhibitor Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 25002028
Inconclusive curation:
>Population AF<1%, gnomAD/1000G
PIK3CA p.Glu545Lys This variant is observed across population databases with max AF< 1% (8.879e-06), which is the threshold used to assume that the variant should be neutral gnomAD combined population: 4.032e-06 gnomAD African/African American: 0 gnomAD Ashkenazi Jewish: 0 gnomAD East Asian: 0 gnomAD European (Finnish): 0 gnomAD European (non-Finnish): 8.879e-06 gnomAD South Asian: 0 gnomAD Other: 0 1000G European: - 1000G African: - 1000G American: - 1000G East Asian: - 1000G South Asian: - >Inconclusive/weaker evidence, ClinVar
PIK3CA p.Glu545Lys https://www.ncbi.nlm.nih.gov/clinvar/variation/2672088 Effect: Pathogenic Allele origin: PIK3CA Review status: criteria provided, single submitter |
Prognostic
> Breast Cancer (CIViC
PIK3CA p.Glu545Lys Disease: Breast Cancer 3 assertions found: https://civicdb.org/links/variants/106 Biomarker: PIK3CA Exon 10 Mutation Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Poor Outcome Drug: n/a Disease: breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 17947469 ──────────────────────── https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Better Outcome Drug: - Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 17575221 ──────────────────────── https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Better Outcome Drug: - Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19671852 |
Tier 2 - Investigational biomarkers: 4
| Gene | Gene Info | Alteration | Functional relevance evidence | Biomarker |
|---|---|---|---|---|
|
ERBB2
|
OG
Oncogene
This gene acts (predominantly) as an oncogene, and thus activating alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
missense
p.Leu755Ser
exon 19/27
more
chr17:37880220 T/C (GRCh37/hg19)
Transcript: ENST00000269571 HGVSp: ENSP00000269571.4:p.Leu755Ser HGVSc: ENST00000269571.5:c.2264T>C Location: exon 19/27 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000406381 HGVSp: ENSP00000385185.2:p.Leu725Ser HGVSc: ENST00000406381.2:c.2174T>C Location: exon 21/29 Consequence: missense variant ──────────────────────── Transcript: ENST00000445658 HGVSp: ENSP00000404047.2:p.Leu479Ser HGVSc: ENST00000445658.2:c.1436T>C Location: exon 13/21 Consequence: missense variant ──────────────────────── Transcript: ENST00000540147 HGVSp: ENSP00000443562.1:p.Leu725Ser HGVSc: ENST00000540147.1:c.2174T>C Location: exon 19/27 Consequence: missense variant ──────────────────────── Transcript: ENST00000541774 HGVSp: ENSP00000446466.1:p.Leu740Ser HGVSc: ENST00000541774.1:c.2219T>C Location: exon 19/27 Consequence: missense variant ──────────────────────── Transcript: ENST00000578373 HGVSp: - HGVSc: ENST00000578373.1:c.*2054T>C Location: exon 19/27 Consequence: 3 prime UTR variant,NMD transcript variant ──────────────────────── Transcript: ENST00000578630 HGVSp: - HGVSc: ENST00000578630.1:n.873T>C Location: exon 5/5 Consequence: non coding transcript exon variant ──────────────────────── Transcript: ENST00000580074 HGVSp: ENSP00000463002.1:p.Leu124Ser HGVSc: ENST00000580074.1:c.371T>C Location: exon 4/6 Consequence: missense variant ──────────────────────── Transcript: ENST00000580969 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant ──────────────────────── Transcript: ENST00000582818 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000582963 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000583038 HGVSp: - HGVSc: ENST00000583038.1:n.3398T>C Location: exon 15/17 Consequence: non coding transcript exon variant ──────────────────────── Transcript: ENST00000584450 HGVSp: ENSP00000463714.1:p.Leu755Ser HGVSc: ENST00000584450.1:c.2264T>C Location: exon 19/26 Consequence: missense variant ──────────────────────── Transcript: ENST00000584601 HGVSp: ENSP00000462438.1:p.Leu725Ser HGVSc: ENST00000584601.1:c.2174T>C Location: exon 23/31 Consequence: missense variant ──────────────────────── Transcript: ENST00000584684 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000584888 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant |
Evidence A (curated):
>Oncogenic, Biomarker, OncoKB
ERBB2 p.Leu755Ser https://oncokb.org/#/gene/ERBB2/alteration/L755S Effect: Oncogenic, Biomarker The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. >Resistance, Sensitivity/Response, CIViC
ERBB2 p.Leu755Ser https://civicdb.org/links/variants/666 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Neratinib Disease: breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28679771 https://civicdb.org/links/variants/666 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Platinum Compound Disease: bladder carcinoma Evidence level: C - Case study Trust rating: 3/5 Source PMID: 25636205 https://civicdb.org/links/variants/39 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Neratinib Disease: breast cancer Evidence level: D - Preclinical Trust rating: 5/5 Source PMID: 23220880 https://civicdb.org/links/variants/39 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Lapatinib Disease: breast cancer Evidence level: D - Preclinical Trust rating: 5/5 Source PMID: 23220880
Inconclusive curation:
>Inconclusive/weaker evidence, ClinVar
ERBB2 p.Leu755Ser https://www.ncbi.nlm.nih.gov/clinvar/variation/376035 Effect: Likely pathogenic Allele origin: ERBB2 Review status: no assertion criteria provided |
Sensitivity/Response
> Neratinib (CIViC; OncoKB
ERBB2 p.Leu755Ser Drug: Neratinib 2 assertions found: https://civicdb.org/links/variants/666 Biomarker: ERBB2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Neratinib Disease: breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28679771 ──────────────────────── https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_3A Drug: Neratinib Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. |
|
PIK3CA
|
OG
Oncogene
This gene acts (predominantly) as an oncogene, and thus activating alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
missense
p.Glu545Lys
exon 10/21
more
chr3:178936091 G/A (GRCh37/hg19)
Transcript: ENST00000263967 HGVSp: ENSP00000263967.3:p.Glu545Lys HGVSc: ENST00000263967.3:c.1633G>A Location: exon 10/21 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000462255 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant |
Evidence A (curated):
>Pathogenic/Likely pathogenic, ClinVar
PIK3CA p.Glu545Lys https://www.ncbi.nlm.nih.gov/clinvar/variation/13655 Effect: Pathogenic/Likely pathogenic Allele origin: PIK3CA Review status: criteria provided, multiple submitters, no conflicts >Oncogenic, Biomarker, OncoKB
PIK3CA p.Glu545Lys https://oncokb.org/#/gene/PIK3CA/alteration/E545K Effect: Oncogenic, Biomarker The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. >Poor Outcome, Resistance, Sensitivity/Response, CIViC
PIK3CA p.Glu545Lys https://civicdb.org/links/variants/106 Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Poor Outcome Drug: n/a Disease: breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 17947469 https://civicdb.org/links/variants/311 Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Better Outcome Drug: - Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 17575221 https://civicdb.org/links/variants/311 Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Better Outcome Drug: - Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19671852 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Fulvestrant,Alpelisib Disease: breast cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 31091374 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Copanlisib Disease: cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 35133871 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28489509 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21594665 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Everolimus Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 27091708 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Lapatinib,Capecitabine Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 26920887 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21594665 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Panitumumab,Cetuximab Disease: colorectal cancer Evidence level: C - Case study Trust rating: 3/5 Source PMID: 19223544 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Aspirin Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 23094721 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Sulindac,Celecoxib,Aspirin Disease: head and neck squamous cell carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 30683736 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Anti-EGFR Monoclonal Antibody Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 23435830 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Erlotinib,Gefitinib Disease: lung non-small cell carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21258250 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Panitumumab,Cetuximab Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19223544 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Cetuximab Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19603024 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Alpelisib Disease: cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 24608574 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 22294718 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Pictilisib Disease: her2-receptor positive breast cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 20453058 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Pictilisib,Akt Inhibitor MK2206 Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 23888070 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab,Lapatinib Disease: her2-receptor positive breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 19010894 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Phosphatidylinositide 3-Kinase Inhibitor,Ribociclib Disease: breast cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 25002028 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: MTOR Kinase Inhibitor PP242,Everolimus Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 21358673 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Palbociclib,Phosphatidylinositide 3-Kinase Inhibitor Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 25002028
Inconclusive curation:
>Population AF<1%, gnomAD/1000G
PIK3CA p.Glu545Lys This variant is observed across population databases with max AF< 1% (8.879e-06), which is the threshold used to assume that the variant should be neutral gnomAD combined population: 4.032e-06 gnomAD African/African American: 0 gnomAD Ashkenazi Jewish: 0 gnomAD East Asian: 0 gnomAD European (Finnish): 0 gnomAD European (non-Finnish): 8.879e-06 gnomAD South Asian: 0 gnomAD Other: 0 1000G European: - 1000G African: - 1000G American: - 1000G East Asian: - 1000G South Asian: - >Inconclusive/weaker evidence, ClinVar
PIK3CA p.Glu545Lys https://www.ncbi.nlm.nih.gov/clinvar/variation/2672088 Effect: Pathogenic Allele origin: PIK3CA Review status: criteria provided, single submitter |
Sensitivity/Response (basket match)
This biomarker is reported to be pan-cancer, and thus it is matched regardless of the tumor type of the sample under analysis.
> Capivasertib (CIViC
PIK3CA p.Glu545Lys Drug: Capivasertib https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28489509 > Copanlisib (CIViC
PIK3CA p.Glu545Lys Drug: Copanlisib https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Copanlisib Disease: cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 35133871 Sensitivity/Response
> Everolimus (CIViC
PIK3CA p.Glu545Lys Drug: Everolimus https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Everolimus Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 27091708 > Lapatinib;Capecitabine (CIViC
PIK3CA p.Glu545Lys Drug: Lapatinib;Capecitabine https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Lapatinib,Capecitabine Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 26920887 > Trastuzumab (CIViC
PIK3CA p.Glu545Lys Drug: Trastuzumab 2 assertions found: https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21594665 ──────────────────────── https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21594665 |
|
ESR1
|
OG
Oncogene
This gene acts (predominantly) as an oncogene, and thus activating alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
missense
p.Tyr537Ser
exon 8/8
more
chr6:152419923 A/C (GRCh37/hg19)
Transcript: ENST00000206249 HGVSp: ENSP00000206249.3:p.Tyr537Ser HGVSc: ENST00000206249.3:c.1610A>C Location: exon 8/8 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000338799 HGVSp: ENSP00000342630.5:p.Tyr537Ser HGVSc: ENST00000338799.5:c.1610A>C Location: exon 9/9 Consequence: missense variant ──────────────────────── Transcript: ENST00000406599 HGVSp: ENSP00000384064.1:p.Tyr276Ser HGVSc: ENST00000406599.1:c.827A>C Location: exon 4/4 Consequence: missense variant ──────────────────────── Transcript: ENST00000427531 HGVSp: - HGVSc: ENST00000427531.2:c.851-26478A>C Location: intron 6/6 Consequence: intron variant ──────────────────────── Transcript: ENST00000440973 HGVSp: ENSP00000405330.1:p.Tyr537Ser HGVSc: ENST00000440973.1:c.1610A>C Location: exon 10/10 Consequence: missense variant ──────────────────────── Transcript: ENST00000443427 HGVSp: ENSP00000387500.1:p.Tyr537Ser HGVSc: ENST00000443427.1:c.1610A>C Location: exon 9/9 Consequence: missense variant ──────────────────────── Transcript: ENST00000456483 HGVSp: ENSP00000415934.2:p.Tyr425Ser HGVSc: ENST00000456483.2:c.1274A>C Location: exon 8/8 Consequence: missense variant |
Evidence A (curated):
>Oncogenic, Biomarker, OncoKB
ESR1 p.Tyr537Ser https://oncokb.org/#/gene/ESR1/alteration/Y537S Effect: Oncogenic, Biomarker The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. >Resistance, Sensitivity/Response, CIViC
ESR1 p.Tyr537Ser https://civicdb.org/links/variants/3910 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Elacestrant Disease: breast cancer Evidence level: A - Guideline Trust rating: 4/5 Source PMID: 35584336 https://civicdb.org/links/variants/50 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Tamoxifen,Fulvestrant Disease: breast cancer Evidence level: D - Preclinical Trust rating: 5/5 Source PMID: 24185510 https://civicdb.org/links/variants/50 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Hormone Therapy Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 24185512 |
Sensitivity/Response
> Fulvestrant (OncoKB
ESR1 p.Tyr537Ser Drug: Fulvestrant 2 assertions found: https://oncokb.org/#/gene/ESR1/alteration/Oncogenic Mutations (excluding Fusions) Biomarker: ESR1 Oncogenic Mutations (excluding Fusions) Effect: drug Responsive Evidence level: LEVEL_3A Drug: Fulvestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/ESR1/alteration/Oncogenic Mutations (excluding Fusions) Biomarker: ESR1 Oncogenic Mutations (excluding Fusions) Effect: drug Responsive Evidence level: LEVEL_3A Drug: Fulvestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. |
|
PIK3CA
|
OG
Oncogene
This gene acts (predominantly) as an oncogene, and thus activating alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
missense
p.Glu545Lys
exon 10/21
more
chr3:178936091 G/A (GRCh37/hg19)
Transcript: ENST00000263967 HGVSp: ENSP00000263967.3:p.Glu545Lys HGVSc: ENST00000263967.3:c.1633G>A Location: exon 10/21 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000462255 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant |
Evidence A (curated):
>Pathogenic/Likely pathogenic, ClinVar
PIK3CA p.Glu545Lys https://www.ncbi.nlm.nih.gov/clinvar/variation/13655 Effect: Pathogenic/Likely pathogenic Allele origin: PIK3CA Review status: criteria provided, multiple submitters, no conflicts >Oncogenic, Biomarker, OncoKB
PIK3CA p.Glu545Lys https://oncokb.org/#/gene/PIK3CA/alteration/E545K Effect: Oncogenic, Biomarker The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. >Poor Outcome, Resistance, Sensitivity/Response, CIViC
PIK3CA p.Glu545Lys https://civicdb.org/links/variants/106 Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Poor Outcome Drug: n/a Disease: breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 17947469 https://civicdb.org/links/variants/311 Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Better Outcome Drug: - Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 17575221 https://civicdb.org/links/variants/311 Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Better Outcome Drug: - Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19671852 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Fulvestrant,Alpelisib Disease: breast cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 31091374 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Copanlisib Disease: cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 35133871 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28489509 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21594665 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Everolimus Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 27091708 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Lapatinib,Capecitabine Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 26920887 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21594665 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Panitumumab,Cetuximab Disease: colorectal cancer Evidence level: C - Case study Trust rating: 3/5 Source PMID: 19223544 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Aspirin Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 23094721 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Sulindac,Celecoxib,Aspirin Disease: head and neck squamous cell carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 30683736 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Anti-EGFR Monoclonal Antibody Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 23435830 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Erlotinib,Gefitinib Disease: lung non-small cell carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21258250 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Panitumumab,Cetuximab Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19223544 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Cetuximab Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19603024 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Alpelisib Disease: cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 24608574 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 22294718 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Pictilisib Disease: her2-receptor positive breast cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 20453058 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Pictilisib,Akt Inhibitor MK2206 Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 23888070 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab,Lapatinib Disease: her2-receptor positive breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 19010894 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Phosphatidylinositide 3-Kinase Inhibitor,Ribociclib Disease: breast cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 25002028 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: MTOR Kinase Inhibitor PP242,Everolimus Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 21358673 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Palbociclib,Phosphatidylinositide 3-Kinase Inhibitor Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 25002028
Inconclusive curation:
>Population AF<1%, gnomAD/1000G
PIK3CA p.Glu545Lys This variant is observed across population databases with max AF< 1% (8.879e-06), which is the threshold used to assume that the variant should be neutral gnomAD combined population: 4.032e-06 gnomAD African/African American: 0 gnomAD Ashkenazi Jewish: 0 gnomAD East Asian: 0 gnomAD European (Finnish): 0 gnomAD European (non-Finnish): 8.879e-06 gnomAD South Asian: 0 gnomAD Other: 0 1000G European: - 1000G African: - 1000G American: - 1000G East Asian: - 1000G South Asian: - >Inconclusive/weaker evidence, ClinVar
PIK3CA p.Glu545Lys https://www.ncbi.nlm.nih.gov/clinvar/variation/2672088 Effect: Pathogenic Allele origin: PIK3CA Review status: criteria provided, single submitter |
Sensitivity/Response (basket match)
This biomarker is reported to be pan-cancer, and thus it is matched regardless of the tumor type of the sample under analysis.
> Capivasertib (CIViC
PIK3CA p.Glu545Lys Drug: Capivasertib https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28489509 > Copanlisib (CIViC
PIK3CA p.Glu545Lys Drug: Copanlisib https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Copanlisib Disease: cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 35133871 Sensitivity/Response
> Everolimus (CIViC
PIK3CA p.Glu545Lys Drug: Everolimus https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Everolimus Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 27091708 > Lapatinib;Capecitabine (CIViC
PIK3CA p.Glu545Lys Drug: Lapatinib;Capecitabine https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Lapatinib,Capecitabine Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 26920887 > Trastuzumab (CIViC
PIK3CA p.Glu545Lys Drug: Trastuzumab 2 assertions found: https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21594665 ──────────────────────── https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21594665 |
Tier 3 - Potential cancer-repurposing opportunities: 2
| Gene | Gene Info | Alteration | Functional relevance evidence | Biomarker |
|---|---|---|---|---|
|
ERBB2
|
OG
Oncogene
This gene acts (predominantly) as an oncogene, and thus activating alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
missense
p.Leu755Ser
exon 19/27
more
chr17:37880220 T/C (GRCh37/hg19)
Transcript: ENST00000269571 HGVSp: ENSP00000269571.4:p.Leu755Ser HGVSc: ENST00000269571.5:c.2264T>C Location: exon 19/27 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000406381 HGVSp: ENSP00000385185.2:p.Leu725Ser HGVSc: ENST00000406381.2:c.2174T>C Location: exon 21/29 Consequence: missense variant ──────────────────────── Transcript: ENST00000445658 HGVSp: ENSP00000404047.2:p.Leu479Ser HGVSc: ENST00000445658.2:c.1436T>C Location: exon 13/21 Consequence: missense variant ──────────────────────── Transcript: ENST00000540147 HGVSp: ENSP00000443562.1:p.Leu725Ser HGVSc: ENST00000540147.1:c.2174T>C Location: exon 19/27 Consequence: missense variant ──────────────────────── Transcript: ENST00000541774 HGVSp: ENSP00000446466.1:p.Leu740Ser HGVSc: ENST00000541774.1:c.2219T>C Location: exon 19/27 Consequence: missense variant ──────────────────────── Transcript: ENST00000578373 HGVSp: - HGVSc: ENST00000578373.1:c.*2054T>C Location: exon 19/27 Consequence: 3 prime UTR variant,NMD transcript variant ──────────────────────── Transcript: ENST00000578630 HGVSp: - HGVSc: ENST00000578630.1:n.873T>C Location: exon 5/5 Consequence: non coding transcript exon variant ──────────────────────── Transcript: ENST00000580074 HGVSp: ENSP00000463002.1:p.Leu124Ser HGVSc: ENST00000580074.1:c.371T>C Location: exon 4/6 Consequence: missense variant ──────────────────────── Transcript: ENST00000580969 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant ──────────────────────── Transcript: ENST00000582818 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000582963 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000583038 HGVSp: - HGVSc: ENST00000583038.1:n.3398T>C Location: exon 15/17 Consequence: non coding transcript exon variant ──────────────────────── Transcript: ENST00000584450 HGVSp: ENSP00000463714.1:p.Leu755Ser HGVSc: ENST00000584450.1:c.2264T>C Location: exon 19/26 Consequence: missense variant ──────────────────────── Transcript: ENST00000584601 HGVSp: ENSP00000462438.1:p.Leu725Ser HGVSc: ENST00000584601.1:c.2174T>C Location: exon 23/31 Consequence: missense variant ──────────────────────── Transcript: ENST00000584684 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000584888 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant |
Evidence A (curated):
>Oncogenic, Biomarker, OncoKB
ERBB2 p.Leu755Ser https://oncokb.org/#/gene/ERBB2/alteration/L755S Effect: Oncogenic, Biomarker The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. >Resistance, Sensitivity/Response, CIViC
ERBB2 p.Leu755Ser https://civicdb.org/links/variants/666 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Neratinib Disease: breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28679771 https://civicdb.org/links/variants/666 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Platinum Compound Disease: bladder carcinoma Evidence level: C - Case study Trust rating: 3/5 Source PMID: 25636205 https://civicdb.org/links/variants/39 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Neratinib Disease: breast cancer Evidence level: D - Preclinical Trust rating: 5/5 Source PMID: 23220880 https://civicdb.org/links/variants/39 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Lapatinib Disease: breast cancer Evidence level: D - Preclinical Trust rating: 5/5 Source PMID: 23220880
Inconclusive curation:
>Inconclusive/weaker evidence, ClinVar
ERBB2 p.Leu755Ser https://www.ncbi.nlm.nih.gov/clinvar/variation/376035 Effect: Likely pathogenic Allele origin: ERBB2 Review status: no assertion criteria provided |
Sensitivity/Response
> Ado-Trastuzumab Emtansine (OncoKB
ERBB2 p.Leu755Ser Drug: Ado-Trastuzumab Emtansine https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Ado-Trastuzumab Emtansine Disease: Non-Small Cell Lung Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Neratinib (OncoKB
ERBB2 p.Leu755Ser Drug: Neratinib 2 assertions found: https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_3A Drug: Neratinib Disease: Non-Small Cell Lung Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Neratinib Disease: Cervical Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Platinum Compound (CIViC
ERBB2 p.Leu755Ser Drug: Platinum Compound https://civicdb.org/links/variants/666 Biomarker: ERBB2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Platinum Compound Disease: bladder carcinoma Evidence level: C - Case study Trust rating: 3/5 Source PMID: 25636205 > Sevabertinib (OncoKB
ERBB2 p.Leu755Ser Drug: Sevabertinib 2 assertions found: https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_3A Drug: Sevabertinib Disease: Non-Small Cell Lung Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/ERBB2/alteration/L726F, L841V, L726I, T733I, L768S, L755A, Exon 20 in-frame insertions, L755P, L755S, L755W, D821N, D769H, D769Y, G776S, G776V, V777L, V777M, V794M, T798M, D808N, V773L, G815R, L866M, I767M, V842I, L869R Biomarker: ERBB2 L726F, L841V, L726I, T733I, L768S, L755A, Exon 20 in-frame insertions, L755P, L755S, L755W, D821N, D769H, D769Y, G776S, G776V, V777L, V777M, V794M, T798M, D808N, V773L, G815R, L866M, I767M, V842I, L869R Effect: drug Responsive Evidence level: LEVEL_1 Drug: Sevabertinib Disease: Non-Small Cell Lung Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Trastuzumab Deruxtecan (OncoKB
ERBB2 p.Leu755Ser Drug: Trastuzumab Deruxtecan https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Trastuzumab Deruxtecan Disease: Non-Small Cell Lung Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Trastuzumab; Pertuzumab; Docetaxel (OncoKB
ERBB2 p.Leu755Ser Drug: Trastuzumab; Pertuzumab; Docetaxel https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_3A Drug: Trastuzumab;Pertuzumab;Docetaxel Disease: Non-Small Cell Lung Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Zongertinib (OncoKB
ERBB2 p.Leu755Ser Drug: Zongertinib 2 assertions found: https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Zongertinib Disease: Non-Small Cell Lung Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/ERBB2/alteration/L726F, L841V, L726I, T733I, L768S, L755A, Exon 20 in-frame insertions, L755P, L755S, L755W, D821N, D769H, D769Y, G776S, G776V, V777L, V777M, V794M, T798M, D808N, V773L, G815R, L866M, I767M, V842I, L869R Biomarker: ERBB2 L726F, L841V, L726I, T733I, L768S, L755A, Exon 20 in-frame insertions, L755P, L755S, L755W, D821N, D769H, D769Y, G776S, G776V, V777L, V777M, V794M, T798M, D808N, V773L, G815R, L866M, I767M, V842I, L869R Effect: drug Responsive Evidence level: LEVEL_1 Drug: Zongertinib Disease: Non-Small Cell Lung Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. |
|
PIK3CA
|
OG
Oncogene
This gene acts (predominantly) as an oncogene, and thus activating alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
missense
p.Glu545Lys
exon 10/21
more
chr3:178936091 G/A (GRCh37/hg19)
Transcript: ENST00000263967 HGVSp: ENSP00000263967.3:p.Glu545Lys HGVSc: ENST00000263967.3:c.1633G>A Location: exon 10/21 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000462255 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant |
Evidence A (curated):
>Pathogenic/Likely pathogenic, ClinVar
PIK3CA p.Glu545Lys https://www.ncbi.nlm.nih.gov/clinvar/variation/13655 Effect: Pathogenic/Likely pathogenic Allele origin: PIK3CA Review status: criteria provided, multiple submitters, no conflicts >Oncogenic, Biomarker, OncoKB
PIK3CA p.Glu545Lys https://oncokb.org/#/gene/PIK3CA/alteration/E545K Effect: Oncogenic, Biomarker The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. >Poor Outcome, Resistance, Sensitivity/Response, CIViC
PIK3CA p.Glu545Lys https://civicdb.org/links/variants/106 Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Poor Outcome Drug: n/a Disease: breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 17947469 https://civicdb.org/links/variants/311 Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Better Outcome Drug: - Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 17575221 https://civicdb.org/links/variants/311 Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Better Outcome Drug: - Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19671852 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Fulvestrant,Alpelisib Disease: breast cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 31091374 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Copanlisib Disease: cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 35133871 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28489509 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21594665 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Everolimus Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 27091708 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Lapatinib,Capecitabine Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 26920887 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21594665 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Panitumumab,Cetuximab Disease: colorectal cancer Evidence level: C - Case study Trust rating: 3/5 Source PMID: 19223544 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Aspirin Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 23094721 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Sulindac,Celecoxib,Aspirin Disease: head and neck squamous cell carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 30683736 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Anti-EGFR Monoclonal Antibody Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 23435830 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Erlotinib,Gefitinib Disease: lung non-small cell carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21258250 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Panitumumab,Cetuximab Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19223544 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Cetuximab Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19603024 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Alpelisib Disease: cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 24608574 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 22294718 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Pictilisib Disease: her2-receptor positive breast cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 20453058 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Pictilisib,Akt Inhibitor MK2206 Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 23888070 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab,Lapatinib Disease: her2-receptor positive breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 19010894 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Phosphatidylinositide 3-Kinase Inhibitor,Ribociclib Disease: breast cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 25002028 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: MTOR Kinase Inhibitor PP242,Everolimus Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 21358673 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Palbociclib,Phosphatidylinositide 3-Kinase Inhibitor Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 25002028
Inconclusive curation:
>Population AF<1%, gnomAD/1000G
PIK3CA p.Glu545Lys This variant is observed across population databases with max AF< 1% (8.879e-06), which is the threshold used to assume that the variant should be neutral gnomAD combined population: 4.032e-06 gnomAD African/African American: 0 gnomAD Ashkenazi Jewish: 0 gnomAD East Asian: 0 gnomAD European (Finnish): 0 gnomAD European (non-Finnish): 8.879e-06 gnomAD South Asian: 0 gnomAD Other: 0 1000G European: - 1000G African: - 1000G American: - 1000G East Asian: - 1000G South Asian: - >Inconclusive/weaker evidence, ClinVar
PIK3CA p.Glu545Lys https://www.ncbi.nlm.nih.gov/clinvar/variation/2672088 Effect: Pathogenic Allele origin: PIK3CA Review status: criteria provided, single submitter |
Sensitivity/Response
> Anti-EGFR Monoclonal Antibody (CIViC
PIK3CA p.Glu545Lys Drug: Anti-EGFR Monoclonal Antibody https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Anti-EGFR Monoclonal Antibody Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 23435830 > Aspirin (CIViC
PIK3CA p.Glu545Lys Drug: Aspirin https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Aspirin Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 23094721 > Cetuximab (CIViC
PIK3CA p.Glu545Lys Drug: Cetuximab https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Cetuximab Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19603024 > Erlotinib;Gefitinib (CIViC
PIK3CA p.Glu545Lys Drug: Erlotinib;Gefitinib https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Erlotinib,Gefitinib Disease: lung non-small cell carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21258250 > Panitumumab;Cetuximab (CIViC
PIK3CA p.Glu545Lys Drug: Panitumumab;Cetuximab 2 assertions found: https://civicdb.org/links/variants/104 Biomarker: PIK3CA E545K Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Panitumumab,Cetuximab Disease: colorectal cancer Evidence level: C - Case study Trust rating: 3/5 Source PMID: 19223544 ──────────────────────── https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Panitumumab,Cetuximab Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19223544 > Sulindac;Celecoxib;Aspirin (CIViC
PIK3CA p.Glu545Lys Drug: Sulindac;Celecoxib;Aspirin https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Sulindac,Celecoxib,Aspirin Disease: head and neck squamous cell carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 30683736 |
Tier 4 - Hypothetical preclinical biomarkers: 4
| Gene | Gene Info | Alteration | Functional relevance evidence | Biomarker |
|---|---|---|---|---|
|
ERBB2
|
OG
Oncogene
This gene acts (predominantly) as an oncogene, and thus activating alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
missense
p.Leu755Ser
exon 19/27
more
chr17:37880220 T/C (GRCh37/hg19)
Transcript: ENST00000269571 HGVSp: ENSP00000269571.4:p.Leu755Ser HGVSc: ENST00000269571.5:c.2264T>C Location: exon 19/27 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000406381 HGVSp: ENSP00000385185.2:p.Leu725Ser HGVSc: ENST00000406381.2:c.2174T>C Location: exon 21/29 Consequence: missense variant ──────────────────────── Transcript: ENST00000445658 HGVSp: ENSP00000404047.2:p.Leu479Ser HGVSc: ENST00000445658.2:c.1436T>C Location: exon 13/21 Consequence: missense variant ──────────────────────── Transcript: ENST00000540147 HGVSp: ENSP00000443562.1:p.Leu725Ser HGVSc: ENST00000540147.1:c.2174T>C Location: exon 19/27 Consequence: missense variant ──────────────────────── Transcript: ENST00000541774 HGVSp: ENSP00000446466.1:p.Leu740Ser HGVSc: ENST00000541774.1:c.2219T>C Location: exon 19/27 Consequence: missense variant ──────────────────────── Transcript: ENST00000578373 HGVSp: - HGVSc: ENST00000578373.1:c.*2054T>C Location: exon 19/27 Consequence: 3 prime UTR variant,NMD transcript variant ──────────────────────── Transcript: ENST00000578630 HGVSp: - HGVSc: ENST00000578630.1:n.873T>C Location: exon 5/5 Consequence: non coding transcript exon variant ──────────────────────── Transcript: ENST00000580074 HGVSp: ENSP00000463002.1:p.Leu124Ser HGVSc: ENST00000580074.1:c.371T>C Location: exon 4/6 Consequence: missense variant ──────────────────────── Transcript: ENST00000580969 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant ──────────────────────── Transcript: ENST00000582818 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000582963 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000583038 HGVSp: - HGVSc: ENST00000583038.1:n.3398T>C Location: exon 15/17 Consequence: non coding transcript exon variant ──────────────────────── Transcript: ENST00000584450 HGVSp: ENSP00000463714.1:p.Leu755Ser HGVSc: ENST00000584450.1:c.2264T>C Location: exon 19/26 Consequence: missense variant ──────────────────────── Transcript: ENST00000584601 HGVSp: ENSP00000462438.1:p.Leu725Ser HGVSc: ENST00000584601.1:c.2174T>C Location: exon 23/31 Consequence: missense variant ──────────────────────── Transcript: ENST00000584684 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000584888 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant |
Evidence A (curated):
>Oncogenic, Biomarker, OncoKB
ERBB2 p.Leu755Ser https://oncokb.org/#/gene/ERBB2/alteration/L755S Effect: Oncogenic, Biomarker The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. >Resistance, Sensitivity/Response, CIViC
ERBB2 p.Leu755Ser https://civicdb.org/links/variants/666 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Neratinib Disease: breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28679771 https://civicdb.org/links/variants/666 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Platinum Compound Disease: bladder carcinoma Evidence level: C - Case study Trust rating: 3/5 Source PMID: 25636205 https://civicdb.org/links/variants/39 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Neratinib Disease: breast cancer Evidence level: D - Preclinical Trust rating: 5/5 Source PMID: 23220880 https://civicdb.org/links/variants/39 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Lapatinib Disease: breast cancer Evidence level: D - Preclinical Trust rating: 5/5 Source PMID: 23220880
Inconclusive curation:
>Inconclusive/weaker evidence, ClinVar
ERBB2 p.Leu755Ser https://www.ncbi.nlm.nih.gov/clinvar/variation/376035 Effect: Likely pathogenic Allele origin: ERBB2 Review status: no assertion criteria provided |
Sensitivity/Response
> Lapatinib (CIViC
ERBB2 p.Leu755Ser Drug: Lapatinib https://civicdb.org/links/variants/39 Biomarker: ERBB2 L755S Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Lapatinib Disease: breast cancer Evidence level: D - Preclinical Trust rating: 5/5 Source PMID: 23220880 > Neratinib (CIViC
ERBB2 p.Leu755Ser Drug: Neratinib https://civicdb.org/links/variants/39 Biomarker: ERBB2 L755S Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Neratinib Disease: breast cancer Evidence level: D - Preclinical Trust rating: 5/5 Source PMID: 23220880 |
|
PIK3CA
|
OG
Oncogene
This gene acts (predominantly) as an oncogene, and thus activating alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
missense
p.Glu545Lys
exon 10/21
more
chr3:178936091 G/A (GRCh37/hg19)
Transcript: ENST00000263967 HGVSp: ENSP00000263967.3:p.Glu545Lys HGVSc: ENST00000263967.3:c.1633G>A Location: exon 10/21 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000462255 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant |
Evidence A (curated):
>Pathogenic/Likely pathogenic, ClinVar
PIK3CA p.Glu545Lys https://www.ncbi.nlm.nih.gov/clinvar/variation/13655 Effect: Pathogenic/Likely pathogenic Allele origin: PIK3CA Review status: criteria provided, multiple submitters, no conflicts >Oncogenic, Biomarker, OncoKB
PIK3CA p.Glu545Lys https://oncokb.org/#/gene/PIK3CA/alteration/E545K Effect: Oncogenic, Biomarker The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. >Poor Outcome, Resistance, Sensitivity/Response, CIViC
PIK3CA p.Glu545Lys https://civicdb.org/links/variants/106 Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Poor Outcome Drug: n/a Disease: breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 17947469 https://civicdb.org/links/variants/311 Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Better Outcome Drug: - Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 17575221 https://civicdb.org/links/variants/311 Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Better Outcome Drug: - Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19671852 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Fulvestrant,Alpelisib Disease: breast cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 31091374 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Copanlisib Disease: cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 35133871 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28489509 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21594665 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Everolimus Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 27091708 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Lapatinib,Capecitabine Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 26920887 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21594665 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Panitumumab,Cetuximab Disease: colorectal cancer Evidence level: C - Case study Trust rating: 3/5 Source PMID: 19223544 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Aspirin Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 23094721 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Sulindac,Celecoxib,Aspirin Disease: head and neck squamous cell carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 30683736 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Anti-EGFR Monoclonal Antibody Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 23435830 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Erlotinib,Gefitinib Disease: lung non-small cell carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21258250 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Panitumumab,Cetuximab Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19223544 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Cetuximab Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19603024 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Alpelisib Disease: cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 24608574 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 22294718 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Pictilisib Disease: her2-receptor positive breast cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 20453058 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Pictilisib,Akt Inhibitor MK2206 Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 23888070 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab,Lapatinib Disease: her2-receptor positive breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 19010894 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Phosphatidylinositide 3-Kinase Inhibitor,Ribociclib Disease: breast cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 25002028 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: MTOR Kinase Inhibitor PP242,Everolimus Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 21358673 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Palbociclib,Phosphatidylinositide 3-Kinase Inhibitor Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 25002028
Inconclusive curation:
>Population AF<1%, gnomAD/1000G
PIK3CA p.Glu545Lys This variant is observed across population databases with max AF< 1% (8.879e-06), which is the threshold used to assume that the variant should be neutral gnomAD combined population: 4.032e-06 gnomAD African/African American: 0 gnomAD Ashkenazi Jewish: 0 gnomAD East Asian: 0 gnomAD European (Finnish): 0 gnomAD European (non-Finnish): 8.879e-06 gnomAD South Asian: 0 gnomAD Other: 0 1000G European: - 1000G African: - 1000G American: - 1000G East Asian: - 1000G South Asian: - >Inconclusive/weaker evidence, ClinVar
PIK3CA p.Glu545Lys https://www.ncbi.nlm.nih.gov/clinvar/variation/2672088 Effect: Pathogenic Allele origin: PIK3CA Review status: criteria provided, single submitter |
Sensitivity/Response (basket match)
This biomarker is reported to be pan-cancer, and thus it is matched regardless of the tumor type of the sample under analysis.
> Alpelisib (CIViC
PIK3CA p.Glu545Lys Drug: Alpelisib https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Alpelisib Disease: cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 24608574 > Capivasertib (CIViC
PIK3CA p.Glu545Lys Drug: Capivasertib https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 22294718 > RLY-2608 (OncoKB
PIK3CA p.Glu545Lys Drug: RLY-2608 https://oncokb.org/#/gene/PIK3CA/alteration/Oncogenic Mutations Biomarker: PIK3CA Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_4 Drug: RLY-2608 Disease: SOLID The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. Sensitivity/Response
> MTOR Kinase Inhibitor PP242;Everolimus (CIViC
PIK3CA p.Glu545Lys Drug: MTOR Kinase Inhibitor PP242;Everolimus https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: MTOR Kinase Inhibitor PP242,Everolimus Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 21358673 > Palbociclib;Phosphatidylinositide 3-Kinase Inhibitor (CIViC
PIK3CA p.Glu545Lys Drug: Palbociclib;Phosphatidylinositide 3-Kinase Inhibitor https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Palbociclib,Phosphatidylinositide 3-Kinase Inhibitor Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 25002028 > Phosphatidylinositide 3-Kinase Inhibitor;Ribociclib (CIViC
PIK3CA p.Glu545Lys Drug: Phosphatidylinositide 3-Kinase Inhibitor;Ribociclib https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Phosphatidylinositide 3-Kinase Inhibitor,Ribociclib Disease: breast cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 25002028 > Pictilisib (CIViC
PIK3CA p.Glu545Lys Drug: Pictilisib https://civicdb.org/links/variants/104 Biomarker: PIK3CA E545K Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Pictilisib Disease: her2-receptor positive breast cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 20453058 > Pictilisib;Akt Inhibitor MK2206 (CIViC
PIK3CA p.Glu545Lys Drug: Pictilisib;Akt Inhibitor MK2206 https://civicdb.org/links/variants/104 Biomarker: PIK3CA E545K Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Pictilisib,Akt Inhibitor MK2206 Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 23888070 > RLY-2608; Fulvestrant (OncoKB
PIK3CA p.Glu545Lys Drug: RLY-2608; Fulvestrant https://oncokb.org/#/gene/PIK3CA/alteration/Oncogenic Mutations Biomarker: PIK3CA Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_4 Drug: RLY-2608;Fulvestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Trastuzumab;Lapatinib (CIViC
PIK3CA p.Glu545Lys Drug: Trastuzumab;Lapatinib https://civicdb.org/links/variants/104 Biomarker: PIK3CA E545K Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab,Lapatinib Disease: her2-receptor positive breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 19010894 |
|
ESR1
|
OG
Oncogene
This gene acts (predominantly) as an oncogene, and thus activating alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
missense
p.Tyr537Ser
exon 8/8
more
chr6:152419923 A/C (GRCh37/hg19)
Transcript: ENST00000206249 HGVSp: ENSP00000206249.3:p.Tyr537Ser HGVSc: ENST00000206249.3:c.1610A>C Location: exon 8/8 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000338799 HGVSp: ENSP00000342630.5:p.Tyr537Ser HGVSc: ENST00000338799.5:c.1610A>C Location: exon 9/9 Consequence: missense variant ──────────────────────── Transcript: ENST00000406599 HGVSp: ENSP00000384064.1:p.Tyr276Ser HGVSc: ENST00000406599.1:c.827A>C Location: exon 4/4 Consequence: missense variant ──────────────────────── Transcript: ENST00000427531 HGVSp: - HGVSc: ENST00000427531.2:c.851-26478A>C Location: intron 6/6 Consequence: intron variant ──────────────────────── Transcript: ENST00000440973 HGVSp: ENSP00000405330.1:p.Tyr537Ser HGVSc: ENST00000440973.1:c.1610A>C Location: exon 10/10 Consequence: missense variant ──────────────────────── Transcript: ENST00000443427 HGVSp: ENSP00000387500.1:p.Tyr537Ser HGVSc: ENST00000443427.1:c.1610A>C Location: exon 9/9 Consequence: missense variant ──────────────────────── Transcript: ENST00000456483 HGVSp: ENSP00000415934.2:p.Tyr425Ser HGVSc: ENST00000456483.2:c.1274A>C Location: exon 8/8 Consequence: missense variant |
Evidence A (curated):
>Oncogenic, Biomarker, OncoKB
ESR1 p.Tyr537Ser https://oncokb.org/#/gene/ESR1/alteration/Y537S Effect: Oncogenic, Biomarker The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. >Resistance, Sensitivity/Response, CIViC
ESR1 p.Tyr537Ser https://civicdb.org/links/variants/3910 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Elacestrant Disease: breast cancer Evidence level: A - Guideline Trust rating: 4/5 Source PMID: 35584336 https://civicdb.org/links/variants/50 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Tamoxifen,Fulvestrant Disease: breast cancer Evidence level: D - Preclinical Trust rating: 5/5 Source PMID: 24185510 https://civicdb.org/links/variants/50 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Hormone Therapy Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 24185512 |
Sensitivity/Response
> Hormone Therapy (CIViC
ESR1 p.Tyr537Ser Drug: Hormone Therapy https://civicdb.org/links/variants/50 Biomarker: ESR1 Y537S Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Hormone Therapy Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 24185512 > Tamoxifen;Fulvestrant (CIViC
ESR1 p.Tyr537Ser Drug: Tamoxifen;Fulvestrant https://civicdb.org/links/variants/50 Biomarker: ESR1 Y537S Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Tamoxifen,Fulvestrant Disease: breast cancer Evidence level: D - Preclinical Trust rating: 5/5 Source PMID: 24185510 |
|
PIK3CA
|
OG
Oncogene
This gene acts (predominantly) as an oncogene, and thus activating alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
missense
p.Glu545Lys
exon 10/21
more
chr3:178936091 G/A (GRCh37/hg19)
Transcript: ENST00000263967 HGVSp: ENSP00000263967.3:p.Glu545Lys HGVSc: ENST00000263967.3:c.1633G>A Location: exon 10/21 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000462255 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant |
Evidence A (curated):
>Pathogenic/Likely pathogenic, ClinVar
PIK3CA p.Glu545Lys https://www.ncbi.nlm.nih.gov/clinvar/variation/13655 Effect: Pathogenic/Likely pathogenic Allele origin: PIK3CA Review status: criteria provided, multiple submitters, no conflicts >Oncogenic, Biomarker, OncoKB
PIK3CA p.Glu545Lys https://oncokb.org/#/gene/PIK3CA/alteration/E545K Effect: Oncogenic, Biomarker The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. >Poor Outcome, Resistance, Sensitivity/Response, CIViC
PIK3CA p.Glu545Lys https://civicdb.org/links/variants/106 Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Poor Outcome Drug: n/a Disease: breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 17947469 https://civicdb.org/links/variants/311 Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Better Outcome Drug: - Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 17575221 https://civicdb.org/links/variants/311 Evidence type: Prognostic Evidence direction: Supports Variant origin: Somatic Clinical significance: Better Outcome Drug: - Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19671852 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Fulvestrant,Alpelisib Disease: breast cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 31091374 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Copanlisib Disease: cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 35133871 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28489509 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21594665 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Everolimus Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 27091708 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Lapatinib,Capecitabine Disease: her2-receptor positive breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 26920887 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab Disease: breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21594665 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Panitumumab,Cetuximab Disease: colorectal cancer Evidence level: C - Case study Trust rating: 3/5 Source PMID: 19223544 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Aspirin Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 23094721 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Sulindac,Celecoxib,Aspirin Disease: head and neck squamous cell carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 30683736 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Anti-EGFR Monoclonal Antibody Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 23435830 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Erlotinib,Gefitinib Disease: lung non-small cell carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21258250 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Panitumumab,Cetuximab Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19223544 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Cetuximab Disease: colorectal cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 19603024 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Alpelisib Disease: cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 24608574 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 22294718 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Pictilisib Disease: her2-receptor positive breast cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 20453058 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Pictilisib,Akt Inhibitor MK2206 Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 23888070 https://civicdb.org/links/variants/104 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab,Lapatinib Disease: her2-receptor positive breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 19010894 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Phosphatidylinositide 3-Kinase Inhibitor,Ribociclib Disease: breast cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 25002028 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: MTOR Kinase Inhibitor PP242,Everolimus Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 21358673 https://civicdb.org/links/variants/311 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Palbociclib,Phosphatidylinositide 3-Kinase Inhibitor Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 25002028
Inconclusive curation:
>Population AF<1%, gnomAD/1000G
PIK3CA p.Glu545Lys This variant is observed across population databases with max AF< 1% (8.879e-06), which is the threshold used to assume that the variant should be neutral gnomAD combined population: 4.032e-06 gnomAD African/African American: 0 gnomAD Ashkenazi Jewish: 0 gnomAD East Asian: 0 gnomAD European (Finnish): 0 gnomAD European (non-Finnish): 8.879e-06 gnomAD South Asian: 0 gnomAD Other: 0 1000G European: - 1000G African: - 1000G American: - 1000G East Asian: - 1000G South Asian: - >Inconclusive/weaker evidence, ClinVar
PIK3CA p.Glu545Lys https://www.ncbi.nlm.nih.gov/clinvar/variation/2672088 Effect: Pathogenic Allele origin: PIK3CA Review status: criteria provided, single submitter |
Sensitivity/Response (basket match)
This biomarker is reported to be pan-cancer, and thus it is matched regardless of the tumor type of the sample under analysis.
> Alpelisib (CIViC
PIK3CA p.Glu545Lys Drug: Alpelisib https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Alpelisib Disease: cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 24608574 > Capivasertib (CIViC
PIK3CA p.Glu545Lys Drug: Capivasertib https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 22294718 > RLY-2608 (OncoKB
PIK3CA p.Glu545Lys Drug: RLY-2608 https://oncokb.org/#/gene/PIK3CA/alteration/Oncogenic Mutations Biomarker: PIK3CA Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_4 Drug: RLY-2608 Disease: SOLID The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. Sensitivity/Response
> MTOR Kinase Inhibitor PP242;Everolimus (CIViC
PIK3CA p.Glu545Lys Drug: MTOR Kinase Inhibitor PP242;Everolimus https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: MTOR Kinase Inhibitor PP242,Everolimus Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 21358673 > Palbociclib;Phosphatidylinositide 3-Kinase Inhibitor (CIViC
PIK3CA p.Glu545Lys Drug: Palbociclib;Phosphatidylinositide 3-Kinase Inhibitor https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Palbociclib,Phosphatidylinositide 3-Kinase Inhibitor Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 25002028 > Phosphatidylinositide 3-Kinase Inhibitor;Ribociclib (CIViC
PIK3CA p.Glu545Lys Drug: Phosphatidylinositide 3-Kinase Inhibitor;Ribociclib https://civicdb.org/links/variants/311 Biomarker: PIK3CA Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Phosphatidylinositide 3-Kinase Inhibitor,Ribociclib Disease: breast cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 25002028 > Pictilisib (CIViC
PIK3CA p.Glu545Lys Drug: Pictilisib https://civicdb.org/links/variants/104 Biomarker: PIK3CA E545K Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Pictilisib Disease: her2-receptor positive breast cancer Evidence level: D - Preclinical Trust rating: 4/5 Source PMID: 20453058 > Pictilisib;Akt Inhibitor MK2206 (CIViC
PIK3CA p.Glu545Lys Drug: Pictilisib;Akt Inhibitor MK2206 https://civicdb.org/links/variants/104 Biomarker: PIK3CA E545K Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Pictilisib,Akt Inhibitor MK2206 Disease: breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 23888070 > RLY-2608; Fulvestrant (OncoKB
PIK3CA p.Glu545Lys Drug: RLY-2608; Fulvestrant https://oncokb.org/#/gene/PIK3CA/alteration/Oncogenic Mutations Biomarker: PIK3CA Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_4 Drug: RLY-2608;Fulvestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Trastuzumab;Lapatinib (CIViC
PIK3CA p.Glu545Lys Drug: Trastuzumab;Lapatinib https://civicdb.org/links/variants/104 Biomarker: PIK3CA E545K Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Resistance Drug: Trastuzumab,Lapatinib Disease: her2-receptor positive breast cancer Evidence level: D - Preclinical Trust rating: 3/5 Source PMID: 19010894 |
Alterations not classified as functional: 1
| Gene | Gene Info | Alteration | Functional classification | Functional relevance evidence | Biomarker |
|---|---|---|---|---|---|
|
CBFB
|
TS
Tumor Suppressor
This gene acts (predominantly) as a tumor suppressor, and thus loss-of-function (or dominant-negative) alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
missense
p.Asp128Val
exon 4/6
more
chr16:67100685 A/T (GRCh37/hg19)
Transcript: ENST00000290858 HGVSp: ENSP00000290858.6:p.Asp128Val HGVSc: ENST00000290858.6:c.383A>T Location: exon 4/6 Consequence: missense variant ──────────────────────── Transcript: ENST00000412916 HGVSp: ENSP00000415151.2:p.Asp128Val HGVSc: ENST00000412916.2:c.383A>T Location: exon 4/6 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000561924 HGVSp: ENSP00000462273.1:p.Asp28Val HGVSc: ENST00000561924.2:c.83A>T Location: exon 4/6 Consequence: missense variant ──────────────────────── Transcript: ENST00000563939 HGVSp: ENSP00000462148.1:p.Asp28Val HGVSc: ENST00000563939.2:c.83A>T Location: exon 3/4 Consequence: missense variant ──────────────────────── Transcript: ENST00000564034 HGVSp: ENSP00000456637.1:p.Asp89Val HGVSc: ENST00000564034.1:c.266A>T Location: exon 3/3 Consequence: missense variant ──────────────────────── Transcript: ENST00000565389 HGVSp: - HGVSc: ENST00000565389.1:c.113-31928A>T Location: intron 2/2 Consequence: intron variant ──────────────────────── Transcript: ENST00000567947 HGVSp: - HGVSc: ENST00000567947.1:n.430A>T Location: exon 2/2 Consequence: non coding transcript exon variant |
Unknown significance |
Inconclusive curation:
>No conclusive criteria, more
CBFB p.Asp128Val No conclusive effect for this variant is reported by the knowledgebases employed here. No biological bona fide assumption or bioinformatic prediction (see PMID: 35221333) applies and/or is conclusive to classify the variant. On detail for this variant, no |
Not contemplated
Potential match with cancer biomarkers is only contemplated for variants that are classified as functionally relevant.
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Proteomics lung cancer subtype: 3
Select reference set(s) for outlier analysis:
Relative protein-set abundance
BRAF
HIGH
-4
-3
-2
-1
0
1