Gene Variant Detail

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Gene BRAF
Variant G469V
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions BRAF G469V is a hotspot mutation within the protein kinase domain of the Braf protein (UniProt.org). G469V results in increased Braf kinase activity and activation of downstream MEK and ERK in cell culture (PMID: 28947956, PMID: 26343582, PMID: 28783719), and in one of two cell lines, increased cell proliferation and cell viability compared to wild-type Braf (PMID: 29533785).
Associated Drug Resistance
Category Variants Paths

BRAF mutant BRAF G469X BRAF G469V

BRAF mutant BRAF act mut BRAF G469V

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Transcript NM_004333.5
gDNA chr7:g.140781602C>A
cDNA c.1406G>T
Protein p.G469V
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004333.5 chr7:g.140781602C>A c.1406G>T p.G469V RefSeq GRCh38/hg38
NM_001354609.1 chr7:g.140781602C>A c.1406G>T p.G469V RefSeq GRCh38/hg38
NM_004333 chr7:g.140781602C>A c.1406G>T p.G469V RefSeq GRCh38/hg38
XM_005250045 chr7:g.140781602C>A c.1406G>T p.G469V RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF G469V Advanced Solid Tumor resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF G469V (PMID: 26343582). 26343582
BRAF G469V lung non-small cell carcinoma predicted - sensitive Sorafenib Case Reports/Case Series Actionable In a clinical case study, a patient with synchronous BRAF wild-type hepatocellular carcinoma (HCC) and non-small cell lung cancer harboring BRAF G469V demonstrated a partial response in primary lung lesions, complete response in the lung metastasis, and stability of the HCC following treatment with Nexavar (sorafenib) (PMID: 27388325). 27388325
BRAF G469V melanoma no benefit Encorafenib Preclinical - Cell culture Actionable In a preclinical study, Braftovi (encorafenib) did not inhibit ERK phosphorylation or proliferation of a melanoma cell line harboring BRAF G469V (PMID: 29903896). 29903896
BRAF G469V lung non-small cell carcinoma no benefit Vemurafenib Case Reports/Case Series Actionable In a Phase II trial, Zelboraf (vemurafenib) treatment did not result in response in the cohort of 15 non-small cell lung cancer patients with non-V600 BRAF mutations, which included 1 patient harboring BRAF G469V, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). 31959346
BRAF G469V osteosarcoma no benefit Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in a patient with osteosarcoma of the renal pelvis harboring BRAF G469V (PMID: 31924734; NCT02465060). 31924734
BRAF G469V lung adenocarcinoma no benefit Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, a previously treated lung adenocarcinoma patient harboring BRAF G469V demonstrated progression after 9 weeks of treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) (PMID: 32540409). 32540409
BRAF G469V colorectal cancer not predictive Fluorouracil + Leucovorin + Oxaliplatin + Panitumumab Case Reports/Case Series Actionable In a clinical study, the combination of Vectibix (panitumumab) with FOLFOX as a first-line therapy resulted in a partial response with progression-free survival of 18.9 months in a patient with metastatic colorectal cancer harboring BRAF G469V (PMID: 31515458). 31515458
BRAF G469V colorectal cancer not predictive Cetuximab + Irinotecan Case Reports/Case Series Actionable In a clinical study, the combination of Erbitux (cetuximab) with Camptosar (irinotecan) as a third-line therapy resulted in stable disease with progression-free survival of 10.9 months in a patient with metastatic colorectal cancer harboring BRAF G469V (PMID: 31515458). 31515458