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Gene | BRAF |
Variant | G469R |
Impact List | missense |
Protein Effect | gain of function - predicted |
Gene Variant Descriptions | BRAF G469R is a hotspot mutation within the protein kinase domain of the Braf protein (UniProt.org). G469R demonstrates intermediate BRAF kinase activity (PMID: 28783719), results in constitutive ERK activation in cell culture (PMID: 24920063), and in one of two cell lines leads to increased cell proliferation and cell viability compared to wild-type Braf (PMID: 29533785), and therefore, is predicted to lead to a gain of Braf protein function. |
Associated Drug Resistance | |
Category Variants Paths |
BRAF mutant BRAF act mut BRAF G469R BRAF mutant BRAF G469X BRAF G469R |
Transcript | NM_004333.6 |
gDNA | chr7:g.140781603C>T |
cDNA | c.1405G>A |
Protein | p.G469R |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001378470.1 | chr7:g.140778001C>T | c.1405G>A | p.G469R | RefSeq | GRCh38/hg38 |
NM_004333.6 | chr7:g.140781603C>T | c.1405G>A | p.G469R | RefSeq | GRCh38/hg38 |
NM_001378467.1 | chr7:g.140781612C>T | c.1405G>A | p.G469R | RefSeq | GRCh38/hg38 |
NM_004333 | chr7:g.140781603C>T | c.1405G>A | p.G469R | RefSeq | GRCh38/hg38 |
NM_001354609.1 | chr7:g.140781603C>T | c.1405G>A | p.G469R | RefSeq | GRCh38/hg38 |
NM_001378468.1 | chr7:g.140781603C>T | c.1405G>A | p.G469R | RefSeq | GRCh38/hg38 |
XM_005250045 | chr7:g.140781603C>T | c.1405G>A | p.G469R | RefSeq | GRCh38/hg38 |
NM_004333.5 | chr7:g.140781603C>T | c.1405G>A | p.G469R | RefSeq | GRCh38/hg38 |
NM_001378474.1 | chr7:g.140781603C>T | c.1405G>A | p.G469R | RefSeq | GRCh38/hg38 |
NM_001354609.2 | chr7:g.140781603C>T | c.1405G>A | p.G469R | RefSeq | GRCh38/hg38 |
XM_047420769.1 | chr7:g.140781603C>T | c.1405G>A | p.G469R | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF G469R | large cell neuroendocrine carcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a durable response in a patient with large cell neuroendocrine carcinoma of the lung harboring BRAF G469R, along with ERBB4 (HER4) A118S, STK11 L282fs, TP53 R248L and MYC amplification and led to a decrease in BRAF G469R in cell-free DNA (PMID: 35135105). | 35135105 |