MTBP

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Unknown Patient •

Analysis run date: 11/27/2025 10:26 • Pipeline version: 7.6.1

Stage: [NA]

Age: 64

Sex: [NA]

Smoking: [NA]

Identifier: [NA]

Hospital: KS

OncoTree: [NA]

WHO2015: [NA]

Purity: [NA]

Tumor Mutation Burden: [NA]

mRNA subtype: [NA]

Proteome subtype: [NA]

2 non-relevant events not shown in the report (e.g. when a variant maps to both strands, the one with no representative gene/transcript) Download

Hide variants in non-cancer genes

Putative functionally relevant variants: 8

Gene	Alteration	Origin	Functional relevance evidence	Custom clinical flags	Biomarker
KRAS 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. SF Secondary Findings Pathogenic variants of germline origin in this gene are recommended to be reported as secondary findings by the Cancer Core Europe consensus when appropriate.	Mutation missense p.Gly12Cys exon 2/5 more Transcript Information Transcript: ENST00000256078 HGVSp: ENSP00000256078.4:p.Gly12Cys HGVSc: ENST00000256078.4:c.34G>T Location: exon 2/6 Consequence: missense variant ──────────────────────── Transcript: ENST00000311936 HGVSp: ENSP00000308495.3:p.Gly12Cys HGVSc: ENST00000311936.3:c.34G>T Location: exon 2/5 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000556131 HGVSp: ENSP00000451856.1:p.Gly12Cys HGVSc: ENST00000556131.1:c.34G>T Location: exon 2/3 Consequence: missense variant ──────────────────────── Transcript: ENST00000557334 HGVSp: ENSP00000452512.1:p.Gly12Cys HGVSc: ENST00000557334.1:c.34G>T Location: exon 2/3 Consequence: missense variant	Tumor Somatic Tumor VAF: n/a	Evidence A (curated): >Oncogenic, Biomarker, OncoKB KRAS p.Gly12Cys https://oncokb.org/#/gene/KRAS/alteration/G12C Effect: Oncogenic, Biomarker >Diagnostic, Poor Outcome, Resistance, Sensitivity/Response, CIViC KRAS p.Gly12Cys https://civicdb.org/links/variants/78 Variant origin: KRAS https://civicdb.org/links/variants/78 Variant origin: KRAS https://civicdb.org/links/variants/78 Variant origin: KRAS https://civicdb.org/links/variants/78 Variant origin: KRAS https://civicdb.org/links/variants/78 Variant origin: KRAS https://civicdb.org/links/variants/78 Variant origin: KRAS https://civicdb.org/links/variants/76 Variant origin: KRAS https://civicdb.org/links/variants/76 Variant origin: KRAS https://civicdb.org/links/variants/76 Variant origin: KRAS https://civicdb.org/links/variants/76 Variant origin: KRAS https://civicdb.org/links/variants/75 Variant origin: KRAS https://civicdb.org/links/variants/75 Variant origin: KRAS https://civicdb.org/links/variants/75 Variant origin: KRAS https://civicdb.org/links/variants/75 Variant origin: KRAS https://civicdb.org/links/variants/75 Variant origin: KRAS Inconclusive curation: >Inconclusive/weaker evidence, ClinVar KRAS p.Gly12Cys https://www.ncbi.nlm.nih.gov/clinvar/variation/12578 Effect: Likely pathogenic Allele origin: KRAS Review status: criteria provided, single submitter https://www.ncbi.nlm.nih.gov/clinvar/variation/1701193 Effect: Pathogenic Allele origin: KRAS Review status: criteria provided, single submitter	None found	Others - Disease Diagnostic, 4 assertions Alterations reported to be diagnostic biomarkers. All diagnostic biomarkers are listed here regardless of whether they refer to the cancer type of the sample under analysis. Please check the original assertions* provided by each knowledgebase listed below* https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Drug: - Disease: Early T-Cell Precursor Lymphoblastic Leukemia Abstracts: n/a https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Drug: - Disease: Juvenile Myelomonocytic Leukemia Abstracts: n/a https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Drug: - Disease: Myelodysplastic Syndromes Abstracts: n/a https://civicdb.org/links/variants/76 Biomarker: KRAS G12 Drug: n/a Disease: acute leukemia Alterations reported to be diagnostic biomarkers. All diagnostic biomarkers are listed here regardless of whether they refer to the cancer type of the sample under analysis. Tier 3-Cancer repurposing, 46 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: Abemaciclib; Adagrasib; Atezolizumab; Bevacizumab; Binimetinib; Cetuximab; Chemotherapy; Cobimetinib; Docetaxel; Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor; Erlotinib; Gefitinib; Gemcitabine; KRAS G12C Inhibitor GDC-6036; Nivolumab; Panitumumab; Pemetrexed; Selumetinib; Sotorasib; Trametinib; Trastuzumab; Tucatinib https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Drug: Adagrasib Disease: Gastrointestinal Neuroendocrine Tumor Abstracts: Bekaii-Saab et al. Abstract# 519, ASCO GI Symposium, 2022 https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Drug: Trametinib Disease: Histiocytosis Abstracts: n/a https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Drug: Cobimetinib Disease: Histiocytosis Abstracts: n/a https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Drug: Trametinib Disease: Histiocytosis Abstracts: n/a https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Drug: Trametinib Disease: Histiocytosis Abstracts: n/a https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Drug: Trametinib Disease: Histiocytosis Abstracts: n/a https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Drug: Cobimetinib Disease: Histiocytosis Abstracts: n/a https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Drug: Cobimetinib Disease: Histiocytosis Abstracts: n/a https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Drug: Cobimetinib Disease: Histiocytosis Abstracts: n/a https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Drug: Tucatinib,Trastuzumab Disease: Colorectal Cancer Abstracts: n/a https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Drug: Panitumumab Disease: Colorectal Cancer Abstracts: n/a https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Drug: Cetuximab Disease: Colorectal Cancer Abstracts: n/a https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Drug: Adagrasib Disease: Esophagogastric Cancer Abstracts: Bekaii-Saab et al. Abstract# 519, ASCO GI Symposium, 2022 https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Drug: Adagrasib Disease: Tubular Adenoma of the Colon Abstracts: Bekaii-Saab et al. Abstract# 519, ASCO GI Symposium, 2022 https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Drug: Adagrasib Disease: Hepatobiliary Cancer Abstracts: Bekaii-Saab et al. Abstract# 519, ASCO GI Symposium, 2022 https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Drug: Sotorasib,Panitumumab Disease: Colorectal Cancer Abstracts: n/a https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Drug: Sotorasib,Cetuximab Disease: Colorectal Cancer Abstracts: n/a https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Drug: Sotorasib Disease: Pancreatic Cancer Abstracts: Strickler et al. Abstract# 360490, ASCO GI 2022 https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Drug: Adagrasib,Panitumumab Disease: Colorectal Cancer Abstracts: n/a https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Drug: Adagrasib Disease: Ampullary Cancer Abstracts: n/a https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Drug: Sotorasib Disease: Ampullary Cancer Abstracts: n/a https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Drug: Adagrasib Disease: Pancreatic Cancer Abstracts: Pant et al. Abstract # 425082, ASCO Monthly Plenary Series April 2023 https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Drug: Adagrasib Disease: Non-Small Cell Lung Cancer Abstracts: Gadgeel et al. Abstract# MA06.04, Journal of Thoracic Oncology Vol. 18 https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Drug: Sotorasib Disease: Non-Small Cell Lung Cancer Abstracts: n/a https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Drug: Adagrasib,Cetuximab Disease: Colorectal Cancer Abstracts: n/a https://civicdb.org/links/variants/78 Biomarker: KRAS G12C Drug: Erlotinib,Gefitinib Disease: colorectal cancer https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Drug: Pemetrexed,Trametinib,Docetaxel Disease: lung non-small cell carcinoma https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Drug: Abemaciclib Disease: lung non-small cell carcinoma https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Drug: Erlotinib Disease: lung non-small cell carcinoma https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Drug: Chemotherapy,Cetuximab Disease: colorectal cancer https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Drug: Docetaxel,Selumetinib Disease: lung non-small cell carcinoma https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Drug: Gefitinib,Erlotinib Disease: lung non-small cell carcinoma https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Drug: Chemotherapy,Bevacizumab Disease: colorectal cancer https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Drug: Docetaxel,Selumetinib Disease: lung non-small cell carcinoma https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Drug: Nivolumab,Atezolizumab Disease: lung non-small cell carcinoma https://civicdb.org/links/variants/75 Biomarker: KRAS Exon 2 Mutation Drug: Gemcitabine,Erlotinib Disease: pancreatic cancer https://civicdb.org/links/variants/75 Biomarker: KRAS Exon 2 Mutation Drug: Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Disease: colorectal cancer https://civicdb.org/links/variants/75 Biomarker: KRAS Exon 2 Mutation Drug: Cetuximab Disease: colorectal cancer https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Drug: Adagrasib Disease: Anal Cancer Abstracts: Bekaii-Saab et al. Abstract# 519, ASCO GI Symposium, 2022 https://civicdb.org/links/variants/78 Biomarker: KRAS G12C Drug: Cetuximab,Chemotherapy Disease: colorectal cancer https://civicdb.org/links/variants/78 Biomarker: KRAS G12C Drug: Sotorasib Disease: lung non-small cell carcinoma https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Drug: Binimetinib Disease: ovary serous adenocarcinoma https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Drug: Cetuximab,Panitumumab Disease: colorectal cancer https://civicdb.org/links/variants/78 Biomarker: KRAS G12C Drug: KRAS G12C Inhibitor GDC-6036 Disease: lung non-small cell carcinoma https://civicdb.org/links/variants/75 Biomarker: KRAS Exon 2 Mutation Drug: Cetuximab Disease: colorectal cancer https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Drug: Adagrasib Disease: Small Bowel Cancer Abstracts: Bekaii-Saab et al. Abstract# 519, ASCO GI Symposium, 2022 Tier 4-Hypothet. (basket match), 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: ARS-853; AZD5438; Binimetinib; Cobimetinib; Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor; G-573; MEK Inhibitor GDC-0623; Trametinib https://civicdb.org/links/variants/78 Biomarker: KRAS G12C Drug: Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor,ARS-853 Disease: cancer https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Drug: Trametinib Disease: SOLID Abstracts: n/a https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Drug: Cobimetinib Disease: SOLID Abstracts: n/a https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Drug: AZD5438 Disease: cancer https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Drug: MEK Inhibitor GDC-0623,G-573 Disease: cancer https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Drug: Trametinib Disease: cancer https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Drug: Binimetinib Disease: SOLID Abstracts: n/a
CAD-ALK 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.	Rearrangement Rearrangement - Fusion	Alteration Details more > Alteration type: TRA > Region: x:xxxx-x:xxxx	Evidence A (curated): >Likely Oncogenic, Biomarker, OncoKB Unknown https://oncokb.org/#/gene/ALK/alteration/CAD-ALK Fusion Effect: Likely Oncogenic, Biomarker	None found	Others - Disease Diagnostic, 2 assertions Alterations reported to be diagnostic biomarkers. All diagnostic biomarkers are listed here regardless of whether they refer to the cancer type of the sample under analysis. Please check the original assertions* provided by each knowledgebase listed below* https://oncokb.org/#/gene/ALK/alteration/Fusions Biomarker: ALK Fusions Drug: - Disease: Anaplastic Large-Cell Lymphoma ALK Positive Abstracts: n/a https://oncokb.org/#/gene/ALK/alteration/Fusions Biomarker: ALK Fusions Drug: - Disease: ALK Positive Large B-Cell Lymphoma Abstracts: n/a Alterations reported to be diagnostic biomarkers. All diagnostic biomarkers are listed here regardless of whether they refer to the cancer type of the sample under analysis. Tier 3-Cancer repurposing, 11 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: Alectinib; Brigatinib; Ceritinib; Crizotinib; Lorlatinib https://oncokb.org/#/gene/ALK/alteration/Fusions Biomarker: ALK Fusions Drug: Lorlatinib Disease: Soft Tissue Sarcoma Abstracts: n/a https://oncokb.org/#/gene/ALK/alteration/Fusions Biomarker: ALK Fusions Drug: Alectinib Disease: Soft Tissue Sarcoma Abstracts: n/a https://oncokb.org/#/gene/ALK/alteration/Fusions Biomarker: ALK Fusions Drug: Crizotinib Disease: Mature T and NK Neoplasms Abstracts: n/a https://oncokb.org/#/gene/ALK/alteration/Fusions Biomarker: ALK Fusions Drug: Crizotinib Disease: Soft Tissue Sarcoma Abstracts: Trahair et al. JCO PO, 2018 https://oncokb.org/#/gene/ALK/alteration/Fusions Biomarker: ALK Fusions Drug: Crizotinib Disease: Non-Small Cell Lung Cancer Abstracts: n/a https://oncokb.org/#/gene/ALK/alteration/Fusions Biomarker: ALK Fusions Drug: Ceritinib Disease: Non-Small Cell Lung Cancer Abstracts: Chow et al. Abstract# 1478O, ESMO 2019 https://oncokb.org/#/gene/ALK/alteration/Fusions Biomarker: ALK Fusions Drug: Alectinib Disease: Non-Small Cell Lung Cancer Abstracts: n/a https://oncokb.org/#/gene/ALK/alteration/Fusions Biomarker: ALK Fusions Drug: Brigatinib Disease: Non-Small Cell Lung Cancer Abstracts: n/a https://oncokb.org/#/gene/ALK/alteration/Fusions Biomarker: ALK Fusions Drug: Lorlatinib Disease: Non-Small Cell Lung Cancer Abstracts: n/a https://oncokb.org/#/gene/ALK/alteration/Fusions Biomarker: ALK Fusions Drug: Ceritinib Disease: Soft Tissue Sarcoma Abstracts: n/a https://oncokb.org/#/gene/ALK/alteration/Fusions Biomarker: ALK Fusions Drug: Brigatinib Disease: Soft Tissue Sarcoma Abstracts: n/a
CDK12 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.Arg882Leu exon 7/14 more Transcript Information Transcript: ENST00000430627 HGVSp: ENSP00000407720.2:p.Arg882Leu HGVSc: ENST00000430627.2:c.2645G>T Location: exon 7/14 Consequence: missense variant ──────────────────────── Transcript: ENST00000447079 HGVSp: ENSP00000398880.3:p.Arg882Leu HGVSc: ENST00000447079.4:c.2645G>T Location: exon 7/14 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000584632 HGVSp: ENSP00000464641.1:p.Arg881Leu HGVSc: ENST00000584632.1:c.2642G>T Location: exon 7/13 Consequence: missense variant	Tumor Somatic Tumor VAF: n/a	Evidence A (curated): >Likely Oncogenic, OncoKB CDK12 p.Arg882Leu https://oncokb.org/#/gene/CDK12/alteration/R882L Effect: Likely Oncogenic	None found	Tier 3-Cancer repurposing, 5 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: Enzalutamide; Olaparib; Talazoparib https://oncokb.org/#/gene/CDK12/alteration/Oncogenic Mutations Biomarker: CDK12 Oncogenic Mutations Drug: Olaparib Disease: Prostate Cancer, NOS Abstracts: n/a https://oncokb.org/#/gene/CDK12/alteration/Oncogenic Mutations Biomarker: CDK12 Oncogenic Mutations Drug: Olaparib Disease: Prostate Cancer Abstracts: n/a https://oncokb.org/#/gene/CDK12/alteration/Oncogenic Mutations Biomarker: CDK12 Oncogenic Mutations Drug: Talazoparib,Enzalutamide Disease: Prostate Cancer Abstracts: n/a https://oncokb.org/#/gene/CDK12/alteration/Oncogenic Mutations Biomarker: CDK12 Oncogenic Mutations Drug: Talazoparib,Enzalutamide Disease: Prostate Cancer, NOS Abstracts: n/a https://civicdb.org/links/variants/2764 Biomarker: CDK12 Mutation Drug: Olaparib Disease: castration-resistant prostate carcinoma
CDKN2A 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.	Copy Number Alt	Alteration Details more > Alteration type: Focal deletion event > Estimated number of gene copies: 0 > Affected region: chr1:9999-999	Evidence A (curated): >Oncogenic, Biomarker, OncoKB CDKN2A https://oncokb.org/#/gene/CDKN2A/alteration/Deletion Effect: Oncogenic, Biomarker	None found	Others - Disease Diagnostic, 3 assertions Alterations reported to be diagnostic biomarkers. All diagnostic biomarkers are listed here regardless of whether they refer to the cancer type of the sample under analysis. Please check the original assertions* provided by each knowledgebase listed below* https://oncokb.org/#/gene/CDKN2A/alteration/Deletion Biomarker: CDKN2A Deletion Drug: - Disease: AML with BCR-ABL1 Abstracts: n/a https://oncokb.org/#/gene/CDKN2A/alteration/Deletion Biomarker: CDKN2A Deletion Drug: - Disease: B-Lymphoblastic Leukemia/Lymphoma Abstracts: n/a https://oncokb.org/#/gene/CDKN2A/alteration/Deletion Biomarker: CDKN2A Deletion Drug: - Disease: T-Lymphoblastic Leukemia/Lymphoma Abstracts: n/a Alterations reported to be diagnostic biomarkers. All diagnostic biomarkers are listed here regardless of whether they refer to the cancer type of the sample under analysis.
EGFR 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.Ala647Thr exon 17/28 more Transcript Information Transcript: ENST00000275493 HGVSp: ENSP00000275493.2:p.Ala647Thr HGVSc: ENST00000275493.2:c.1939G>A Location: exon 17/28 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000342916 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000344576 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000442591 HGVSp: - HGVSc: ENST00000442591.1:c.28+74G>A Location:* intron 17/17 Consequence: intron variant ──────────────────────── Transcript: ENST00000454757 HGVSp: ENSP00000395243.2:p.Ala594Thr HGVSc: ENST00000454757.2:c.1780G>A Location: exon 17/28 Consequence: missense variant ──────────────────────── Transcript: ENST00000455089 HGVSp: ENSP00000415559.1:p.Ala602Thr HGVSc: ENST00000455089.1:c.1804G>A Location: exon 16/26 Consequence: missense variant	Tumor Somatic Tumor VAF: n/a	Evidence A (curated): >Resistance, OncoKB EGFR p.Ala647Thr https://oncokb.org/#/gene/EGFR/alteration/A647T Effect: Resistance Inconclusive curation: >Population AF<1%, gnomAD/1000G EGFR p.Ala647Thr This variant is observed across population databases with max AF< 1% (3.266e-05), which is the threshold used to assume that the variant should be neutral gnomAD combined population: 0 gnomAD African/African American: 0 gnomAD Ashkenazi Jewish: 0 gnomAD East Asian: 0 gnomAD European (Finnish): 0 gnomAD European (non-Finnish): 0 gnomAD South Asian: 0 gnomAD Other: 0 1000G European: - 1000G African: - 1000G American: - 1000G East Asian: - 1000G South Asian: - >Inconclusive/weaker evidence, ClinVar EGFR p.Ala647Thr https://www.ncbi.nlm.nih.gov/clinvar/variation/839611 Effect: Uncertain significance Allele origin: EGFR Review status: criteria provided, single submitter	None found	Tier 3-Cancer repurposing, 11 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: Afatinib; Cytoreductive Surgery; Erlotinib; Gefitinib; Hyperthermic Intraperitoneal Chemotherapy https://civicdb.org/links/variants/442 Biomarker: EGFR Mutation Drug: Erlotinib Disease: lung non-small cell carcinoma https://civicdb.org/links/variants/442 Biomarker: EGFR Mutation Drug: Hyperthermic Intraperitoneal Chemotherapy,Cytoreductive Surgery Disease: peritoneal mesothelioma https://civicdb.org/links/variants/442 Biomarker: EGFR Mutation Drug: Erlotinib Disease: lung non-small cell carcinoma https://civicdb.org/links/variants/442 Biomarker: EGFR Mutation Drug: Gefitinib Disease: lung non-small cell carcinoma https://civicdb.org/links/variants/442 Biomarker: EGFR Mutation Drug: Gefitinib Disease: lung non-small cell carcinoma https://civicdb.org/links/variants/442 Biomarker: EGFR Mutation Drug: Afatinib Disease: lung non-small cell carcinoma https://civicdb.org/links/variants/442 Biomarker: EGFR Mutation Drug: Gefitinib Disease: lung non-small cell carcinoma https://civicdb.org/links/variants/442 Biomarker: EGFR Mutation Drug: Gefitinib,Erlotinib Disease: lung non-small cell carcinoma https://civicdb.org/links/variants/442 Biomarker: EGFR Mutation Drug: Gefitinib Disease: lung non-small cell carcinoma https://civicdb.org/links/variants/442 Biomarker: EGFR Mutation Drug: Afatinib Disease: lung non-small cell carcinoma https://civicdb.org/links/variants/442 Biomarker: EGFR Mutation Drug: Erlotinib Disease: lung non-small cell carcinoma
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.Arg188Cys exon 4/27 more Transcript Information Transcript: ENST00000269571 HGVSp: ENSP00000269571.4:p.Arg188Cys HGVSc: ENST00000269571.5:c.562C>T Location: exon 4/27 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000406381 HGVSp: ENSP00000385185.2:p.Arg158Cys HGVSc: ENST00000406381.2:c.472C>T Location: exon 6/29 Consequence: missense variant ──────────────────────── Transcript: ENST00000445658 HGVSp: - HGVSc: ENST00000445658.2:c.74-2488C>T Location: intron 1/20 Consequence: intron variant ──────────────────────── Transcript: ENST00000540042 HGVSp: ENSP00000446382.1:p.Arg158Cys HGVSc: ENST00000540042.1:c.472C>T Location: exon 4/15 Consequence: missense variant ──────────────────────── Transcript: ENST00000540147 HGVSp: ENSP00000443562.1:p.Arg158Cys HGVSc: ENST00000540147.1:c.472C>T Location: exon 4/27 Consequence: missense variant ──────────────────────── Transcript: ENST00000541774 HGVSp: ENSP00000446466.1:p.Arg173Cys HGVSc: ENST00000541774.1:c.517C>T Location: exon 4/27 Consequence: missense variant ──────────────────────── Transcript: ENST00000578199 HGVSp: ENSP00000462808.1:p.Arg158Cys HGVSc: ENST00000578199.1:c.472C>T Location: exon 7/18 Consequence: missense variant ──────────────────────── Transcript: ENST00000578373 HGVSp: - HGVSc: ENST00000578373.1:c.352C>T Location:* exon 4/27 Consequence: 3 prime UTR variant,NMD transcript variant ──────────────────────── Transcript: ENST00000578502 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant ──────────────────────── Transcript: ENST00000578709 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000582648 HGVSp: - HGVSc: ENST00000582648.1:c.225+2299C>T Location: intron 2/7 Consequence: intron variant,NMD transcript variant ──────────────────────── Transcript: ENST00000582788 HGVSp: - HGVSc: ENST00000582788.1:n.390+2299C>T Location: intron 2/7 Consequence: intron variant,non coding transcript variant ──────────────────────── Transcript: ENST00000583038 HGVSp: - HGVSc: ENST00000583038.1:n.1254C>T Location: exon 2/17 Consequence: non coding transcript exon variant ──────────────────────── Transcript: ENST00000583391 HGVSp: - HGVSc: ENST00000583391.1:n.197C>T Location: exon 1/4 Consequence: non coding transcript exon variant ──────────────────────── Transcript: ENST00000584099 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000584450 HGVSp: ENSP00000463714.1:p.Arg188Cys HGVSc: ENST00000584450.1:c.562C>T Location: exon 4/26 Consequence: missense variant ──────────────────────── Transcript: ENST00000584601 HGVSp: ENSP00000462438.1:p.Arg158Cys HGVSc: ENST00000584601.1:c.472C>T Location: exon 8/31 Consequence: missense variant ──────────────────────── Transcript: ENST00000584908 HGVSp: - HGVSc: ENST00000584908.1:n.574C>T Location: exon 4/8 Consequence: non coding transcript exon variant	Tumor Somatic Tumor VAF: n/a	Evidence A (curated): >Likely Oncogenic, OncoKB ERBB2 p.Arg188Cys https://oncokb.org/#/gene/ERBB2/alteration/R188C Effect: Likely Oncogenic Inconclusive curation: >Population AF<1%, gnomAD/1000G ERBB2 p.Arg188Cys This variant is observed across population databases with max AF< 1% (3.518e-05), which is the threshold used to assume that the variant should be neutral gnomAD combined population: 0 gnomAD African/African American: 0 gnomAD Ashkenazi Jewish: 0 gnomAD East Asian: 0 gnomAD European (Finnish): 0 gnomAD European (non-Finnish): 0 gnomAD South Asian: 0 gnomAD Other: 0 1000G European: - 1000G African: - 1000G American: - 1000G East Asian: - 1000G South Asian: - >Inconclusive/weaker evidence, ClinVar ERBB2 p.Arg188Cys https://www.ncbi.nlm.nih.gov/clinvar/variation/2169773 Effect: Uncertain significance Allele origin: ERBB2 Review status: criteria provided, single submitter	None found	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: Ado-Trastuzumab Emtansine; Docetaxel; Neratinib; Pertuzumab; Platinum Compound; Trastuzumab; Trastuzumab Deruxtecan https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Drug: Trastuzumab Deruxtecan Disease: Non-Small Cell Lung Cancer Abstracts: n/a https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Drug: Trastuzumab,Pertuzumab,Docetaxel Disease: Non-Small Cell Lung Cancer Abstracts: n/a https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Drug: Neratinib Disease: Non-Small Cell Lung Cancer Abstracts: n/a https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Drug: Neratinib Disease: Breast Cancer Abstracts: n/a https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Drug: Ado-Trastuzumab Emtansine Disease: Non-Small Cell Lung Cancer Abstracts: n/a https://civicdb.org/links/variants/666 Biomarker: ERBB2 Mutation Drug: Platinum Compound Disease: bladder carcinoma https://civicdb.org/links/variants/666 Biomarker: ERBB2 Mutation Drug: Neratinib Disease: breast cancer
MTAP 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.	Copy Number Alt	Alteration Details more > Alteration type: Focal deletion event > Estimated number of gene copies: 0 > Affected region: chr1:9999-999	Evidence B (assumed): >Gene deletion in tumor suppressor, see more MTAP A deletion in a gene (predominantly) acting as tumor suppressor is assumed to be functionally relevant	None found	None found
MYC 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.	Copy Number Alt	Alteration Details more > Alteration type: Focal amplification event > Estimated number of gene copies: 12 > Affected region: chr1:9999-999	Evidence B (assumed): >Gene amplification in oncogene, see more MYC An amplification in a gene (predominantly) acting as oncogene is assumed to be functionally relevant	None found	None found

Variants of unknown/contradictory functional significance: 0

No data available.

Hide variants in non-cancer genes

Special - Other biomarkers of clinical interest: 3

Gene	Alteration	Origin	Functional relevance evidence	Biomarker
KRAS 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. SF Secondary Findings Pathogenic variants of germline origin in this gene are recommended to be reported as secondary findings by the Cancer Core Europe consensus when appropriate.	Mutation missense p.Gly12Cys exon 2/5 more Transcript Information Transcript: ENST00000256078 HGVSp: ENSP00000256078.4:p.Gly12Cys HGVSc: ENST00000256078.4:c.34G>T Location: exon 2/6 Consequence: missense variant ──────────────────────── Transcript: ENST00000311936 HGVSp: ENSP00000308495.3:p.Gly12Cys HGVSc: ENST00000311936.3:c.34G>T Location: exon 2/5 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000556131 HGVSp: ENSP00000451856.1:p.Gly12Cys HGVSc: ENST00000556131.1:c.34G>T Location: exon 2/3 Consequence: missense variant ──────────────────────── Transcript: ENST00000557334 HGVSp: ENSP00000452512.1:p.Gly12Cys HGVSc: ENST00000557334.1:c.34G>T Location: exon 2/3 Consequence: missense variant	Tumor Somatic Tumor VAF: n/a	Evidence A (curated): >Oncogenic, Biomarker, OncoKB KRAS p.Gly12Cys https://oncokb.org/#/gene/KRAS/alteration/G12C Effect: Oncogenic, Biomarker >Diagnostic, Poor Outcome, Resistance, Sensitivity/Response, CIViC KRAS p.Gly12Cys https://civicdb.org/links/variants/78 Variant origin: KRAS https://civicdb.org/links/variants/78 Variant origin: KRAS https://civicdb.org/links/variants/78 Variant origin: KRAS https://civicdb.org/links/variants/78 Variant origin: KRAS https://civicdb.org/links/variants/78 Variant origin: KRAS https://civicdb.org/links/variants/78 Variant origin: KRAS https://civicdb.org/links/variants/76 Variant origin: KRAS https://civicdb.org/links/variants/76 Variant origin: KRAS https://civicdb.org/links/variants/76 Variant origin: KRAS https://civicdb.org/links/variants/76 Variant origin: KRAS https://civicdb.org/links/variants/75 Variant origin: KRAS https://civicdb.org/links/variants/75 Variant origin: KRAS https://civicdb.org/links/variants/75 Variant origin: KRAS https://civicdb.org/links/variants/75 Variant origin: KRAS https://civicdb.org/links/variants/75 Variant origin: KRAS Inconclusive curation: >Inconclusive/weaker evidence, ClinVar KRAS p.Gly12Cys https://www.ncbi.nlm.nih.gov/clinvar/variation/12578 Effect: Likely pathogenic Allele origin: KRAS Review status: criteria provided, single submitter https://www.ncbi.nlm.nih.gov/clinvar/variation/1701193 Effect: Pathogenic Allele origin: KRAS Review status: criteria provided, single submitter	Others - Disease diagnostic > Early T-Cell Precursor Lymphoblastic Leukemia (OncoKB KRAS p.Gly12Cys Disease: Early T-Cell Precursor Lymphoblastic Leukemia https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Effect: Diagnostic Evidence level: LEVEL_Dx3 Drug: - Disease: Early T-Cell Precursor Lymphoblastic Leukemia Abstracts: n/a ) > Juvenile Myelomonocytic Leukemia (OncoKB KRAS p.Gly12Cys Disease: Juvenile Myelomonocytic Leukemia https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Effect: Diagnostic Evidence level: LEVEL_Dx2 Drug: - Disease: Juvenile Myelomonocytic Leukemia Abstracts: n/a ) > Myelodysplastic Syndromes (OncoKB KRAS p.Gly12Cys Disease: Myelodysplastic Syndromes https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Effect: Diagnostic Evidence level: LEVEL_Dx2 Drug: - Disease: Myelodysplastic Syndromes Abstracts: n/a ) > acute leukemia (CIViC KRAS p.Gly12Cys Disease: acute leukemia https://civicdb.org/links/variants/76 Biomarker: KRAS G12 Effect: Diagnostic Drug: n/a Disease: acute leukemia )
CDKN2A 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.	Copy Number Alt	Alteration Details more > Alteration type: Focal deletion event > Estimated number of gene copies: 0 > Affected region: chr1:9999-999	Evidence A (curated): >Oncogenic, Biomarker, OncoKB CDKN2A https://oncokb.org/#/gene/CDKN2A/alteration/Deletion Effect: Oncogenic, Biomarker	Others - Disease diagnostic > AML with BCR-ABL1 (OncoKB CDKN2A Copy Number Alteration (Deletion) Disease: AML with BCR-ABL1 https://oncokb.org/#/gene/CDKN2A/alteration/Deletion Biomarker: CDKN2A Deletion Effect: Diagnostic Evidence level: LEVEL_Dx2 Drug: - Disease: AML with BCR-ABL1 Abstracts: n/a ) > B-Lymphoblastic Leukemia/Lymphoma (OncoKB CDKN2A Copy Number Alteration (Deletion) Disease: B-Lymphoblastic Leukemia/Lymphoma https://oncokb.org/#/gene/CDKN2A/alteration/Deletion Biomarker: CDKN2A Deletion Effect: Diagnostic Evidence level: LEVEL_Dx2 Drug: - Disease: B-Lymphoblastic Leukemia/Lymphoma Abstracts: n/a ) > T-Lymphoblastic Leukemia/Lymphoma (OncoKB CDKN2A Copy Number Alteration (Deletion) Disease: T-Lymphoblastic Leukemia/Lymphoma https://oncokb.org/#/gene/CDKN2A/alteration/Deletion Biomarker: CDKN2A Deletion Effect: Diagnostic Evidence level: LEVEL_Dx2 Drug: - Disease: T-Lymphoblastic Leukemia/Lymphoma Abstracts: n/a )
CAD-ALK 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.	Rearrangement Rearrangement - Fusion	Alteration Details more > Alteration type: TRA > Region: x:xxxx-x:xxxx	Evidence A (curated): >Likely Oncogenic, Biomarker, OncoKB Unknown https://oncokb.org/#/gene/ALK/alteration/CAD-ALK Fusion Effect: Likely Oncogenic, Biomarker	Others - Disease diagnostic > ALK Positive Large B-Cell Lymphoma (OncoKB Unknown Rearrangement - Fusion Disease: ALK Positive Large B-Cell Lymphoma https://oncokb.org/#/gene/ALK/alteration/Fusions Biomarker: ALK Fusions Effect: Diagnostic Evidence level: LEVEL_Dx1 Drug: - Disease: ALK Positive Large B-Cell Lymphoma Abstracts: n/a ) > Anaplastic Large-Cell Lymphoma ALK Positive (OncoKB Unknown Rearrangement - Fusion Disease: Anaplastic Large-Cell Lymphoma ALK Positive https://oncokb.org/#/gene/ALK/alteration/Fusions Biomarker: ALK Fusions Effect: Diagnostic Evidence level: LEVEL_Dx1 Drug: - Disease: Anaplastic Large-Cell Lymphoma ALK Positive Abstracts: n/a )

Tier 3 - Potential cancer-repurposing opportunities: 5

Gene	Alteration	Origin	Functional relevance evidence	Biomarker
KRAS 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. SF Secondary Findings Pathogenic variants of germline origin in this gene are recommended to be reported as secondary findings by the Cancer Core Europe consensus when appropriate.	Mutation missense p.Gly12Cys exon 2/5 more Transcript Information Transcript: ENST00000256078 HGVSp: ENSP00000256078.4:p.Gly12Cys HGVSc: ENST00000256078.4:c.34G>T Location: exon 2/6 Consequence: missense variant ──────────────────────── Transcript: ENST00000311936 HGVSp: ENSP00000308495.3:p.Gly12Cys HGVSc: ENST00000311936.3:c.34G>T Location: exon 2/5 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000556131 HGVSp: ENSP00000451856.1:p.Gly12Cys HGVSc: ENST00000556131.1:c.34G>T Location: exon 2/3 Consequence: missense variant ──────────────────────── Transcript: ENST00000557334 HGVSp: ENSP00000452512.1:p.Gly12Cys HGVSc: ENST00000557334.1:c.34G>T Location: exon 2/3 Consequence: missense variant	Tumor Somatic Tumor VAF: n/a	Evidence A (curated): >Oncogenic, Biomarker, OncoKB KRAS p.Gly12Cys https://oncokb.org/#/gene/KRAS/alteration/G12C Effect: Oncogenic, Biomarker >Diagnostic, Poor Outcome, Resistance, Sensitivity/Response, CIViC KRAS p.Gly12Cys https://civicdb.org/links/variants/78 Variant origin: KRAS https://civicdb.org/links/variants/78 Variant origin: KRAS https://civicdb.org/links/variants/78 Variant origin: KRAS https://civicdb.org/links/variants/78 Variant origin: KRAS https://civicdb.org/links/variants/78 Variant origin: KRAS https://civicdb.org/links/variants/78 Variant origin: KRAS https://civicdb.org/links/variants/76 Variant origin: KRAS https://civicdb.org/links/variants/76 Variant origin: KRAS https://civicdb.org/links/variants/76 Variant origin: KRAS https://civicdb.org/links/variants/76 Variant origin: KRAS https://civicdb.org/links/variants/75 Variant origin: KRAS https://civicdb.org/links/variants/75 Variant origin: KRAS https://civicdb.org/links/variants/75 Variant origin: KRAS https://civicdb.org/links/variants/75 Variant origin: KRAS https://civicdb.org/links/variants/75 Variant origin: KRAS Inconclusive curation: >Inconclusive/weaker evidence, ClinVar KRAS p.Gly12Cys https://www.ncbi.nlm.nih.gov/clinvar/variation/12578 Effect: Likely pathogenic Allele origin: KRAS Review status: criteria provided, single submitter https://www.ncbi.nlm.nih.gov/clinvar/variation/1701193 Effect: Pathogenic Allele origin: KRAS Review status: criteria provided, single submitter	Sensitivity/Response > Abemaciclib (CIViC KRAS p.Gly12Cys Drug: Abemaciclib https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Effect: Sensitivity/Response Drug: Abemaciclib Disease: lung non-small cell carcinoma ) > Adagrasib (OncoKB KRAS p.Gly12Cys Drug: Adagrasib 9 assertions found: https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Effect: Sensitivity/Response Evidence level: LEVEL_3A Drug: Adagrasib Disease: Gastrointestinal Neuroendocrine Tumor Abstracts: Bekaii-Saab et al. Abstract# 519, ASCO GI Symposium, 2022 ──────────────────────── https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Effect: Sensitivity/Response Evidence level: LEVEL_3A Drug: Adagrasib Disease: Esophagogastric Cancer Abstracts: Bekaii-Saab et al. Abstract# 519, ASCO GI Symposium, 2022 ──────────────────────── https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Effect: Sensitivity/Response Evidence level: LEVEL_3A Drug: Adagrasib Disease: Tubular Adenoma of the Colon Abstracts: Bekaii-Saab et al. Abstract# 519, ASCO GI Symposium, 2022 ──────────────────────── https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Effect: Sensitivity/Response Evidence level: LEVEL_3A Drug: Adagrasib Disease: Hepatobiliary Cancer Abstracts: Bekaii-Saab et al. Abstract# 519, ASCO GI Symposium, 2022 ──────────────────────── https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Effect: Sensitivity/Response Evidence level: LEVEL_2 Drug: Adagrasib Disease: Ampullary Cancer Abstracts: n/a ──────────────────────── https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Effect: Sensitivity/Response Evidence level: LEVEL_2 Drug: Adagrasib Disease: Pancreatic Cancer Abstracts: Pant et al. Abstract # 425082, ASCO Monthly Plenary Series April 2023 ──────────────────────── https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Effect: Sensitivity/Response Evidence level: LEVEL_1 Drug: Adagrasib Disease: Non-Small Cell Lung Cancer Abstracts: Gadgeel et al. Abstract# MA06.04, Journal of Thoracic Oncology Vol. 18 ──────────────────────── https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Effect: Sensitivity/Response Evidence level: LEVEL_3A Drug: Adagrasib Disease: Anal Cancer Abstracts: Bekaii-Saab et al. Abstract# 519, ASCO GI Symposium, 2022 ──────────────────────── https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Effect: Sensitivity/Response Evidence level: LEVEL_3A Drug: Adagrasib Disease: Small Bowel Cancer Abstracts: Bekaii-Saab et al. Abstract# 519, ASCO GI Symposium, 2022 ) > Adagrasib; Cetuximab (OncoKB KRAS p.Gly12Cys Drug: Adagrasib; Cetuximab https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Effect: Sensitivity/Response Evidence level: LEVEL_2 Drug: Adagrasib;Cetuximab Disease: Colorectal Cancer Abstracts: n/a ) > Adagrasib; Panitumumab (OncoKB KRAS p.Gly12Cys Drug: Adagrasib; Panitumumab https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Effect: Sensitivity/Response Evidence level: LEVEL_2 Drug: Adagrasib;Panitumumab Disease: Colorectal Cancer Abstracts: n/a ) > Binimetinib (CIViC KRAS p.Gly12Cys Drug: Binimetinib https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Effect: Sensitivity/Response Drug: Binimetinib Disease: ovary serous adenocarcinoma ) > Cetuximab (OncoKB; CIViC KRAS p.Gly12Cys Drug: Cetuximab 3 assertions found: https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Effect: Resistance/reduced sensitivity Evidence level: LEVEL_R1 Drug: Cetuximab Disease: Colorectal Cancer Abstracts: n/a ──────────────────────── https://civicdb.org/links/variants/75 Biomarker: KRAS Exon 2 Mutation Effect: Resistance/reduced sensitivity Drug: Cetuximab Disease: colorectal cancer ──────────────────────── https://civicdb.org/links/variants/75 Biomarker: KRAS Exon 2 Mutation Effect: Resistance/reduced sensitivity Drug: Cetuximab Disease: colorectal cancer ) > Cetuximab;Chemotherapy (CIViC KRAS p.Gly12Cys Drug: Cetuximab;Chemotherapy https://civicdb.org/links/variants/78 Biomarker: KRAS G12C Effect: Resistance/reduced sensitivity Drug: Cetuximab,Chemotherapy Disease: colorectal cancer ) > Cetuximab;Panitumumab (CIViC KRAS p.Gly12Cys Drug: Cetuximab;Panitumumab https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Effect: Resistance/reduced sensitivity Drug: Cetuximab,Panitumumab Disease: colorectal cancer ) > Chemotherapy;Bevacizumab (CIViC KRAS p.Gly12Cys Drug: Chemotherapy;Bevacizumab https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Effect: Resistance/reduced sensitivity Drug: Chemotherapy,Bevacizumab Disease: colorectal cancer ) > Chemotherapy;Cetuximab (CIViC KRAS p.Gly12Cys Drug: Chemotherapy;Cetuximab https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Effect: Resistance/reduced sensitivity Drug: Chemotherapy,Cetuximab Disease: colorectal cancer ) > Cobimetinib (OncoKB KRAS p.Gly12Cys Drug: Cobimetinib 4 assertions found: https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Effect: Sensitivity/Response Evidence level: LEVEL_3A Drug: Cobimetinib Disease: Histiocytosis Abstracts: n/a ──────────────────────── https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Effect: Sensitivity/Response Evidence level: LEVEL_2 Drug: Cobimetinib Disease: Histiocytosis Abstracts: n/a ──────────────────────── https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Effect: Sensitivity/Response Evidence level: LEVEL_2 Drug: Cobimetinib Disease: Histiocytosis Abstracts: n/a ──────────────────────── https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Effect: Sensitivity/Response Evidence level: LEVEL_2 Drug: Cobimetinib Disease: Histiocytosis Abstracts: n/a ) > Docetaxel;Selumetinib (CIViC KRAS p.Gly12Cys Drug: Docetaxel;Selumetinib 2 assertions found: https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Effect: Resistance/reduced sensitivity Drug: Docetaxel,Selumetinib Disease: lung non-small cell carcinoma ──────────────────────── https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Effect: Sensitivity/Response Drug: Docetaxel,Selumetinib Disease: lung non-small cell carcinoma ) > Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (CIViC KRAS p.Gly12Cys Drug: Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor https://civicdb.org/links/variants/75 Biomarker: KRAS Exon 2 Mutation Effect: Resistance/reduced sensitivity Drug: Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Disease: colorectal cancer ) > Erlotinib (CIViC KRAS p.Gly12Cys Drug: Erlotinib https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Effect: Resistance/reduced sensitivity Drug: Erlotinib Disease: lung non-small cell carcinoma ) > Erlotinib;Gefitinib (CIViC KRAS p.Gly12Cys Drug: Erlotinib;Gefitinib https://civicdb.org/links/variants/78 Biomarker: KRAS G12C Effect: Resistance/reduced sensitivity Drug: Erlotinib,Gefitinib Disease: colorectal cancer ) > Gefitinib;Erlotinib (CIViC KRAS p.Gly12Cys Drug: Gefitinib;Erlotinib https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Effect: Resistance/reduced sensitivity Drug: Gefitinib,Erlotinib Disease: lung non-small cell carcinoma ) > Gemcitabine;Erlotinib (CIViC KRAS p.Gly12Cys Drug: Gemcitabine;Erlotinib https://civicdb.org/links/variants/75 Biomarker: KRAS Exon 2 Mutation Effect: Resistance/reduced sensitivity Drug: Gemcitabine,Erlotinib Disease: pancreatic cancer ) > KRAS G12C Inhibitor GDC-6036 (CIViC KRAS p.Gly12Cys Drug: KRAS G12C Inhibitor GDC-6036 https://civicdb.org/links/variants/78 Biomarker: KRAS G12C Effect: Sensitivity/Response Drug: KRAS G12C Inhibitor GDC-6036 Disease: lung non-small cell carcinoma ) > Nivolumab;Atezolizumab (CIViC KRAS p.Gly12Cys Drug: Nivolumab;Atezolizumab https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Effect: Sensitivity/Response Drug: Nivolumab,Atezolizumab Disease: lung non-small cell carcinoma ) > Panitumumab (OncoKB KRAS p.Gly12Cys Drug: Panitumumab https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Effect: Resistance/reduced sensitivity Evidence level: LEVEL_R1 Drug: Panitumumab Disease: Colorectal Cancer Abstracts: n/a ) > Pemetrexed;Trametinib;Docetaxel (CIViC KRAS p.Gly12Cys Drug: Pemetrexed;Trametinib;Docetaxel https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Effect: Sensitivity/Response Drug: Pemetrexed,Trametinib,Docetaxel Disease: lung non-small cell carcinoma ) > Sotorasib (OncoKB; CIViC KRAS p.Gly12Cys Drug: Sotorasib 4 assertions found: https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Effect: Sensitivity/Response Evidence level: LEVEL_2 Drug: Sotorasib Disease: Pancreatic Cancer Abstracts: Strickler et al. Abstract# 360490, ASCO GI 2022 ──────────────────────── https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Effect: Sensitivity/Response Evidence level: LEVEL_2 Drug: Sotorasib Disease: Ampullary Cancer Abstracts: n/a ──────────────────────── https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Effect: Sensitivity/Response Evidence level: LEVEL_1 Drug: Sotorasib Disease: Non-Small Cell Lung Cancer Abstracts: n/a ──────────────────────── https://civicdb.org/links/variants/78 Biomarker: KRAS G12C Effect: Sensitivity/Response Drug: Sotorasib Disease: lung non-small cell carcinoma ) > Sotorasib; Cetuximab (OncoKB KRAS p.Gly12Cys Drug: Sotorasib; Cetuximab https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Effect: Sensitivity/Response Evidence level: LEVEL_2 Drug: Sotorasib;Cetuximab Disease: Colorectal Cancer Abstracts: n/a ) > Sotorasib; Panitumumab (OncoKB KRAS p.Gly12Cys Drug: Sotorasib; Panitumumab https://oncokb.org/#/gene/KRAS/alteration/G12C Biomarker: KRAS G12C Effect: Sensitivity/Response Evidence level: LEVEL_2 Drug: Sotorasib;Panitumumab Disease: Colorectal Cancer Abstracts: n/a ) > Trametinib (OncoKB KRAS p.Gly12Cys Drug: Trametinib 4 assertions found: https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Effect: Sensitivity/Response Evidence level: LEVEL_3A Drug: Trametinib Disease: Histiocytosis Abstracts: n/a ──────────────────────── https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Effect: Sensitivity/Response Evidence level: LEVEL_2 Drug: Trametinib Disease: Histiocytosis Abstracts: n/a ──────────────────────── https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Effect: Sensitivity/Response Evidence level: LEVEL_2 Drug: Trametinib Disease: Histiocytosis Abstracts: n/a ──────────────────────── https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Effect: Sensitivity/Response Evidence level: LEVEL_2 Drug: Trametinib Disease: Histiocytosis Abstracts: n/a ) > Tucatinib; Trastuzumab (OncoKB KRAS p.Gly12Cys Drug: Tucatinib; Trastuzumab https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Effect: Resistance/reduced sensitivity Evidence level: LEVEL_R1 Drug: Tucatinib;Trastuzumab Disease: Colorectal Cancer Abstracts: n/a )
CDK12 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.Arg882Leu exon 7/14 more Transcript Information Transcript: ENST00000430627 HGVSp: ENSP00000407720.2:p.Arg882Leu HGVSc: ENST00000430627.2:c.2645G>T Location: exon 7/14 Consequence: missense variant ──────────────────────── Transcript: ENST00000447079 HGVSp: ENSP00000398880.3:p.Arg882Leu HGVSc: ENST00000447079.4:c.2645G>T Location: exon 7/14 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000584632 HGVSp: ENSP00000464641.1:p.Arg881Leu HGVSc: ENST00000584632.1:c.2642G>T Location: exon 7/13 Consequence: missense variant	Tumor Somatic Tumor VAF: n/a	Evidence A (curated): >Likely Oncogenic, OncoKB CDK12 p.Arg882Leu https://oncokb.org/#/gene/CDK12/alteration/R882L Effect: Likely Oncogenic	Sensitivity/Response > Olaparib (OncoKB; CIViC CDK12 p.Arg882Leu Drug: Olaparib 3 assertions found: https://oncokb.org/#/gene/CDK12/alteration/Oncogenic Mutations Biomarker: CDK12 Oncogenic Mutations Effect: Sensitivity/Response Evidence level: LEVEL_1 Drug: Olaparib Disease: Prostate Cancer, NOS Abstracts: n/a ──────────────────────── https://oncokb.org/#/gene/CDK12/alteration/Oncogenic Mutations Biomarker: CDK12 Oncogenic Mutations Effect: Sensitivity/Response Evidence level: LEVEL_1 Drug: Olaparib Disease: Prostate Cancer Abstracts: n/a ──────────────────────── https://civicdb.org/links/variants/2764 Biomarker: CDK12 Mutation Effect: Sensitivity/Response Drug: Olaparib Disease: castration-resistant prostate carcinoma ) > Talazoparib; Enzalutamide (OncoKB CDK12 p.Arg882Leu Drug: Talazoparib; Enzalutamide 2 assertions found: https://oncokb.org/#/gene/CDK12/alteration/Oncogenic Mutations Biomarker: CDK12 Oncogenic Mutations Effect: Sensitivity/Response Evidence level: LEVEL_1 Drug: Talazoparib;Enzalutamide Disease: Prostate Cancer Abstracts: n/a ──────────────────────── https://oncokb.org/#/gene/CDK12/alteration/Oncogenic Mutations Biomarker: CDK12 Oncogenic Mutations Effect: Sensitivity/Response Evidence level: LEVEL_1 Drug: Talazoparib;Enzalutamide Disease: Prostate Cancer, NOS Abstracts: n/a )
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.Arg188Cys exon 4/27 more Transcript Information Transcript: ENST00000269571 HGVSp: ENSP00000269571.4:p.Arg188Cys HGVSc: ENST00000269571.5:c.562C>T Location: exon 4/27 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000406381 HGVSp: ENSP00000385185.2:p.Arg158Cys HGVSc: ENST00000406381.2:c.472C>T Location: exon 6/29 Consequence: missense variant ──────────────────────── Transcript: ENST00000445658 HGVSp: - HGVSc: ENST00000445658.2:c.74-2488C>T Location: intron 1/20 Consequence: intron variant ──────────────────────── Transcript: ENST00000540042 HGVSp: ENSP00000446382.1:p.Arg158Cys HGVSc: ENST00000540042.1:c.472C>T Location: exon 4/15 Consequence: missense variant ──────────────────────── Transcript: ENST00000540147 HGVSp: ENSP00000443562.1:p.Arg158Cys HGVSc: ENST00000540147.1:c.472C>T Location: exon 4/27 Consequence: missense variant ──────────────────────── Transcript: ENST00000541774 HGVSp: ENSP00000446466.1:p.Arg173Cys HGVSc: ENST00000541774.1:c.517C>T Location: exon 4/27 Consequence: missense variant ──────────────────────── Transcript: ENST00000578199 HGVSp: ENSP00000462808.1:p.Arg158Cys HGVSc: ENST00000578199.1:c.472C>T Location: exon 7/18 Consequence: missense variant ──────────────────────── Transcript: ENST00000578373 HGVSp: - HGVSc: ENST00000578373.1:c.352C>T Location:* exon 4/27 Consequence: 3 prime UTR variant,NMD transcript variant ──────────────────────── Transcript: ENST00000578502 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant ──────────────────────── Transcript: ENST00000578709 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000582648 HGVSp: - HGVSc: ENST00000582648.1:c.225+2299C>T Location: intron 2/7 Consequence: intron variant,NMD transcript variant ──────────────────────── Transcript: ENST00000582788 HGVSp: - HGVSc: ENST00000582788.1:n.390+2299C>T Location: intron 2/7 Consequence: intron variant,non coding transcript variant ──────────────────────── Transcript: ENST00000583038 HGVSp: - HGVSc: ENST00000583038.1:n.1254C>T Location: exon 2/17 Consequence: non coding transcript exon variant ──────────────────────── Transcript: ENST00000583391 HGVSp: - HGVSc: ENST00000583391.1:n.197C>T Location: exon 1/4 Consequence: non coding transcript exon variant ──────────────────────── Transcript: ENST00000584099 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000584450 HGVSp: ENSP00000463714.1:p.Arg188Cys HGVSc: ENST00000584450.1:c.562C>T Location: exon 4/26 Consequence: missense variant ──────────────────────── Transcript: ENST00000584601 HGVSp: ENSP00000462438.1:p.Arg158Cys HGVSc: ENST00000584601.1:c.472C>T Location: exon 8/31 Consequence: missense variant ──────────────────────── Transcript: ENST00000584908 HGVSp: - HGVSc: ENST00000584908.1:n.574C>T Location: exon 4/8 Consequence: non coding transcript exon variant	Tumor Somatic Tumor VAF: n/a	Evidence A (curated): >Likely Oncogenic, OncoKB ERBB2 p.Arg188Cys https://oncokb.org/#/gene/ERBB2/alteration/R188C Effect: Likely Oncogenic Inconclusive curation: >Population AF<1%, gnomAD/1000G ERBB2 p.Arg188Cys This variant is observed across population databases with max AF< 1% (3.518e-05), which is the threshold used to assume that the variant should be neutral gnomAD combined population: 0 gnomAD African/African American: 0 gnomAD Ashkenazi Jewish: 0 gnomAD East Asian: 0 gnomAD European (Finnish): 0 gnomAD European (non-Finnish): 0 gnomAD South Asian: 0 gnomAD Other: 0 1000G European: - 1000G African: - 1000G American: - 1000G East Asian: - 1000G South Asian: - >Inconclusive/weaker evidence, ClinVar ERBB2 p.Arg188Cys https://www.ncbi.nlm.nih.gov/clinvar/variation/2169773 Effect: Uncertain significance Allele origin: ERBB2 Review status: criteria provided, single submitter	Sensitivity/Response > Ado-Trastuzumab Emtansine (OncoKB ERBB2 p.Arg188Cys Drug: Ado-Trastuzumab Emtansine https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Effect: Sensitivity/Response Evidence level: LEVEL_2 Drug: Ado-Trastuzumab Emtansine Disease: Non-Small Cell Lung Cancer Abstracts: n/a ) > Neratinib (OncoKB; CIViC ERBB2 p.Arg188Cys Drug: Neratinib 3 assertions found: https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Effect: Sensitivity/Response Evidence level: LEVEL_3A Drug: Neratinib Disease: Non-Small Cell Lung Cancer Abstracts: n/a ──────────────────────── https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Effect: Sensitivity/Response Evidence level: LEVEL_3A Drug: Neratinib Disease: Breast Cancer Abstracts: n/a ──────────────────────── https://civicdb.org/links/variants/666 Biomarker: ERBB2 Mutation Effect: Sensitivity/Response Drug: Neratinib Disease: breast cancer ) > Platinum Compound (CIViC ERBB2 p.Arg188Cys Drug: Platinum Compound https://civicdb.org/links/variants/666 Biomarker: ERBB2 Mutation Effect: Sensitivity/Response Drug: Platinum Compound Disease: bladder carcinoma ) > Trastuzumab Deruxtecan (OncoKB ERBB2 p.Arg188Cys Drug: Trastuzumab Deruxtecan https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Effect: Sensitivity/Response Evidence level: LEVEL_1 Drug: Trastuzumab Deruxtecan Disease: Non-Small Cell Lung Cancer Abstracts: n/a ) > Trastuzumab; Pertuzumab; Docetaxel (OncoKB ERBB2 p.Arg188Cys Drug: Trastuzumab; Pertuzumab; Docetaxel https://oncokb.org/#/gene/ERBB2/alteration/Oncogenic Mutations Biomarker: ERBB2 Oncogenic Mutations Effect: Sensitivity/Response Evidence level: LEVEL_3A Drug: Trastuzumab;Pertuzumab;Docetaxel Disease: Non-Small Cell Lung Cancer Abstracts: n/a )
EGFR 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.Ala647Thr exon 17/28 more Transcript Information Transcript: ENST00000275493 HGVSp: ENSP00000275493.2:p.Ala647Thr HGVSc: ENST00000275493.2:c.1939G>A Location: exon 17/28 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000342916 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000344576 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000442591 HGVSp: - HGVSc: ENST00000442591.1:c.28+74G>A Location:* intron 17/17 Consequence: intron variant ──────────────────────── Transcript: ENST00000454757 HGVSp: ENSP00000395243.2:p.Ala594Thr HGVSc: ENST00000454757.2:c.1780G>A Location: exon 17/28 Consequence: missense variant ──────────────────────── Transcript: ENST00000455089 HGVSp: ENSP00000415559.1:p.Ala602Thr HGVSc: ENST00000455089.1:c.1804G>A Location: exon 16/26 Consequence: missense variant	Tumor Somatic Tumor VAF: n/a	Evidence A (curated): >Resistance, OncoKB EGFR p.Ala647Thr https://oncokb.org/#/gene/EGFR/alteration/A647T Effect: Resistance Inconclusive curation: >Population AF<1%, gnomAD/1000G EGFR p.Ala647Thr This variant is observed across population databases with max AF< 1% (3.266e-05), which is the threshold used to assume that the variant should be neutral gnomAD combined population: 0 gnomAD African/African American: 0 gnomAD Ashkenazi Jewish: 0 gnomAD East Asian: 0 gnomAD European (Finnish): 0 gnomAD European (non-Finnish): 0 gnomAD South Asian: 0 gnomAD Other: 0 1000G European: - 1000G African: - 1000G American: - 1000G East Asian: - 1000G South Asian: - >Inconclusive/weaker evidence, ClinVar EGFR p.Ala647Thr https://www.ncbi.nlm.nih.gov/clinvar/variation/839611 Effect: Uncertain significance Allele origin: EGFR Review status: criteria provided, single submitter	Sensitivity/Response > Afatinib (CIViC EGFR p.Ala647Thr Drug: Afatinib 2 assertions found: https://civicdb.org/links/variants/442 Biomarker: EGFR Mutation Effect: Sensitivity/Response Drug: Afatinib Disease: lung non-small cell carcinoma ──────────────────────── https://civicdb.org/links/variants/442 Biomarker: EGFR Mutation Effect: Sensitivity/Response Drug: Afatinib Disease: lung non-small cell carcinoma ) > Erlotinib (CIViC EGFR p.Ala647Thr Drug: Erlotinib 3 assertions found: https://civicdb.org/links/variants/442 Biomarker: EGFR Mutation Effect: Sensitivity/Response Drug: Erlotinib Disease: lung non-small cell carcinoma ──────────────────────── https://civicdb.org/links/variants/442 Biomarker: EGFR Mutation Effect: Sensitivity/Response Drug: Erlotinib Disease: lung non-small cell carcinoma ──────────────────────── https://civicdb.org/links/variants/442 Biomarker: EGFR Mutation Effect: Sensitivity/Response Drug: Erlotinib Disease: lung non-small cell carcinoma ) > Gefitinib (CIViC EGFR p.Ala647Thr Drug: Gefitinib 4 assertions found: https://civicdb.org/links/variants/442 Biomarker: EGFR Mutation Effect: Sensitivity/Response Drug: Gefitinib Disease: lung non-small cell carcinoma ──────────────────────── https://civicdb.org/links/variants/442 Biomarker: EGFR Mutation Effect: Sensitivity/Response Drug: Gefitinib Disease: lung non-small cell carcinoma ──────────────────────── https://civicdb.org/links/variants/442 Biomarker: EGFR Mutation Effect: Sensitivity/Response Drug: Gefitinib Disease: lung non-small cell carcinoma ──────────────────────── https://civicdb.org/links/variants/442 Biomarker: EGFR Mutation Effect: Sensitivity/Response Drug: Gefitinib Disease: lung non-small cell carcinoma ) > Gefitinib;Erlotinib (CIViC EGFR p.Ala647Thr Drug: Gefitinib;Erlotinib https://civicdb.org/links/variants/442 Biomarker: EGFR Mutation Effect: Sensitivity/Response Drug: Gefitinib,Erlotinib Disease: lung non-small cell carcinoma ) > Hyperthermic Intraperitoneal Chemotherapy;Cytoreductive Surgery (CIViC EGFR p.Ala647Thr Drug: Hyperthermic Intraperitoneal Chemotherapy;Cytoreductive Surgery https://civicdb.org/links/variants/442 Biomarker: EGFR Mutation Effect: Sensitivity/Response Drug: Hyperthermic Intraperitoneal Chemotherapy,Cytoreductive Surgery Disease: peritoneal mesothelioma )
CAD-ALK 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.	Rearrangement Rearrangement - Fusion	Alteration Details more > Alteration type: TRA > Region: x:xxxx-x:xxxx	Evidence A (curated): >Likely Oncogenic, Biomarker, OncoKB Unknown https://oncokb.org/#/gene/ALK/alteration/CAD-ALK Fusion Effect: Likely Oncogenic, Biomarker	Sensitivity/Response > Alectinib (OncoKB Unknown Rearrangement - Fusion Drug: Alectinib 2 assertions found: https://oncokb.org/#/gene/ALK/alteration/Fusions Biomarker: ALK Fusions Effect: Sensitivity/Response Evidence level: LEVEL_2 Drug: Alectinib Disease: Soft Tissue Sarcoma Abstracts: n/a ──────────────────────── https://oncokb.org/#/gene/ALK/alteration/Fusions Biomarker: ALK Fusions Effect: Sensitivity/Response Evidence level: LEVEL_1 Drug: Alectinib Disease: Non-Small Cell Lung Cancer Abstracts: n/a ) > Brigatinib (OncoKB Unknown Rearrangement - Fusion Drug: Brigatinib 2 assertions found: https://oncokb.org/#/gene/ALK/alteration/Fusions Biomarker: ALK Fusions Effect: Sensitivity/Response Evidence level: LEVEL_1 Drug: Brigatinib Disease: Non-Small Cell Lung Cancer Abstracts: n/a ──────────────────────── https://oncokb.org/#/gene/ALK/alteration/Fusions Biomarker: ALK Fusions Effect: Sensitivity/Response Evidence level: LEVEL_2 Drug: Brigatinib Disease: Soft Tissue Sarcoma Abstracts: n/a ) > Ceritinib (OncoKB Unknown Rearrangement - Fusion Drug: Ceritinib 2 assertions found: https://oncokb.org/#/gene/ALK/alteration/Fusions Biomarker: ALK Fusions Effect: Sensitivity/Response Evidence level: LEVEL_1 Drug: Ceritinib Disease: Non-Small Cell Lung Cancer Abstracts: Chow et al. Abstract# 1478O, ESMO 2019 ──────────────────────── https://oncokb.org/#/gene/ALK/alteration/Fusions Biomarker: ALK Fusions Effect: Sensitivity/Response Evidence level: LEVEL_2 Drug: Ceritinib Disease: Soft Tissue Sarcoma Abstracts: n/a ) > Crizotinib (OncoKB Unknown Rearrangement - Fusion Drug: Crizotinib 3 assertions found: https://oncokb.org/#/gene/ALK/alteration/Fusions Biomarker: ALK Fusions Effect: Sensitivity/Response Evidence level: LEVEL_1 Drug: Crizotinib Disease: Mature T and NK Neoplasms Abstracts: n/a ──────────────────────── https://oncokb.org/#/gene/ALK/alteration/Fusions Biomarker: ALK Fusions Effect: Sensitivity/Response Evidence level: LEVEL_1 Drug: Crizotinib Disease: Soft Tissue Sarcoma Abstracts: Trahair et al. JCO PO, 2018 ──────────────────────── https://oncokb.org/#/gene/ALK/alteration/Fusions Biomarker: ALK Fusions Effect: Sensitivity/Response Evidence level: LEVEL_1 Drug: Crizotinib Disease: Non-Small Cell Lung Cancer Abstracts: n/a ) > Lorlatinib (OncoKB Unknown Rearrangement - Fusion Drug: Lorlatinib 2 assertions found: https://oncokb.org/#/gene/ALK/alteration/Fusions Biomarker: ALK Fusions Effect: Sensitivity/Response Evidence level: LEVEL_2 Drug: Lorlatinib Disease: Soft Tissue Sarcoma Abstracts: n/a ──────────────────────── https://oncokb.org/#/gene/ALK/alteration/Fusions Biomarker: ALK Fusions Effect: Sensitivity/Response Evidence level: LEVEL_1 Drug: Lorlatinib Disease: Non-Small Cell Lung Cancer Abstracts: n/a )

Tier 4 - Hypothetical preclinical biomarkers: 1

Gene	Alteration	Origin	Functional relevance evidence	Biomarker
KRAS 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. SF Secondary Findings Pathogenic variants of germline origin in this gene are recommended to be reported as secondary findings by the Cancer Core Europe consensus when appropriate.	Mutation missense p.Gly12Cys exon 2/5 more Transcript Information Transcript: ENST00000256078 HGVSp: ENSP00000256078.4:p.Gly12Cys HGVSc: ENST00000256078.4:c.34G>T Location: exon 2/6 Consequence: missense variant ──────────────────────── Transcript: ENST00000311936 HGVSp: ENSP00000308495.3:p.Gly12Cys HGVSc: ENST00000311936.3:c.34G>T Location: exon 2/5 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000556131 HGVSp: ENSP00000451856.1:p.Gly12Cys HGVSc: ENST00000556131.1:c.34G>T Location: exon 2/3 Consequence: missense variant ──────────────────────── Transcript: ENST00000557334 HGVSp: ENSP00000452512.1:p.Gly12Cys HGVSc: ENST00000557334.1:c.34G>T Location: exon 2/3 Consequence: missense variant	Tumor Somatic Tumor VAF: n/a	Evidence A (curated): >Oncogenic, Biomarker, OncoKB KRAS p.Gly12Cys https://oncokb.org/#/gene/KRAS/alteration/G12C Effect: Oncogenic, Biomarker >Diagnostic, Poor Outcome, Resistance, Sensitivity/Response, CIViC KRAS p.Gly12Cys https://civicdb.org/links/variants/78 Variant origin: KRAS https://civicdb.org/links/variants/78 Variant origin: KRAS https://civicdb.org/links/variants/78 Variant origin: KRAS https://civicdb.org/links/variants/78 Variant origin: KRAS https://civicdb.org/links/variants/78 Variant origin: KRAS https://civicdb.org/links/variants/78 Variant origin: KRAS https://civicdb.org/links/variants/76 Variant origin: KRAS https://civicdb.org/links/variants/76 Variant origin: KRAS https://civicdb.org/links/variants/76 Variant origin: KRAS https://civicdb.org/links/variants/76 Variant origin: KRAS https://civicdb.org/links/variants/75 Variant origin: KRAS https://civicdb.org/links/variants/75 Variant origin: KRAS https://civicdb.org/links/variants/75 Variant origin: KRAS https://civicdb.org/links/variants/75 Variant origin: KRAS https://civicdb.org/links/variants/75 Variant origin: KRAS Inconclusive curation: >Inconclusive/weaker evidence, ClinVar KRAS p.Gly12Cys https://www.ncbi.nlm.nih.gov/clinvar/variation/12578 Effect: Likely pathogenic Allele origin: KRAS Review status: criteria provided, single submitter https://www.ncbi.nlm.nih.gov/clinvar/variation/1701193 Effect: Pathogenic Allele origin: KRAS Review status: criteria provided, single submitter	Sensitivity/Response (basket match) > AZD5438 (CIViC KRAS p.Gly12Cys Drug: AZD5438 https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Effect: Sensitivity/Response Drug: AZD5438 Disease: cancer ) > Binimetinib (OncoKB KRAS p.Gly12Cys Drug: Binimetinib https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Effect: Sensitivity/Response Evidence level: LEVEL_4 Drug: Binimetinib Disease: SOLID Abstracts: n/a ) > Cobimetinib (OncoKB KRAS p.Gly12Cys Drug: Cobimetinib https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Effect: Sensitivity/Response Evidence level: LEVEL_4 Drug: Cobimetinib Disease: SOLID Abstracts: n/a ) > Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor;ARS-853 (CIViC KRAS p.Gly12Cys Drug: Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor;ARS-853 https://civicdb.org/links/variants/78 Biomarker: KRAS G12C Effect: Sensitivity/Response Drug: Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor,ARS-853 Disease: cancer ) > MEK Inhibitor GDC-0623;G-573 (CIViC KRAS p.Gly12Cys Drug: MEK Inhibitor GDC-0623;G-573 https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Effect: Sensitivity/Response Drug: MEK Inhibitor GDC-0623,G-573 Disease: cancer ) > Trametinib (OncoKB; CIViC KRAS p.Gly12Cys Drug: Trametinib 2 assertions found: https://oncokb.org/#/gene/KRAS/alteration/Oncogenic Mutations Biomarker: KRAS Oncogenic Mutations Effect: Sensitivity/Response Evidence level: LEVEL_4 Drug: Trametinib Disease: SOLID Abstracts: n/a ──────────────────────── https://civicdb.org/links/variants/336 Biomarker: KRAS Mutation Effect: Sensitivity/Response Drug: Trametinib Disease: cancer )

Other functional alterations with no associated biomarkers: 2

Gene	Alteration	Origin	Functional relevance evidence	Biomarker
MTAP 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.	Copy Number Alt	Alteration Details more > Alteration type: Focal deletion event > Estimated number of gene copies: 0 > Affected region: chr1:9999-999	Evidence B (assumed): >Gene deletion in tumor suppressor, see more MTAP A deletion in a gene (predominantly) acting as tumor suppressor is assumed to be functionally relevant	Not contemplated
MYC 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.	Copy Number Alt	Alteration Details more > Alteration type: Focal amplification event > Estimated number of gene copies: 12 > Affected region: chr1:9999-999	Evidence B (assumed): >Gene amplification in oncogene, see more MYC An amplification in a gene (predominantly) acting as oncogene is assumed to be functionally relevant	Not contemplated

Proteomics lung cancer subtype: 3

Select reference set(s) for outlier analysis:

AC (75)

SqCC (32)

LCC (22)

LCNEC (10)

SCLC (2)

Relative protein-set abundance

BRAF

HIGH

-4 -3 -2 -1 0 1

Relative individual protein abundance

No data available.