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Gene | BRAF |
Variant | L597S |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | BRAF L597S lies within the protein kinase domain of the Braf protein (UniProt.org). L597S results in activation of Braf as indicated by increased phosphorylation of Mek and Erk in cell culture (PMID: 22798288) and induces cell proliferation and cell viability in culture (PMID: 29533785). |
Associated Drug Resistance | |
Category Variants Paths |
BRAF mutant BRAF act mut BRAF L597S BRAF mutant BRAF L597X BRAF L597S |
Transcript | NM_004333.6 |
gDNA | chr7:g.140753345_140753346delCTinsTC |
cDNA | c.1789_1790delCTinsTC |
Protein | p.L597S |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001378468.1 | chr7:g.140753345_140753346delCTinsTC | c.1789_1790delCTinsTC | p.L597S | RefSeq | GRCh38/hg38 |
NM_004333 | chr7:g.140753345_140753346delAGinsGA | c.1789_1790delCTinsTC | p.L597S | RefSeq | GRCh38/hg38 |
NM_001378472.1 | chr7:g.140749333A>G | c.1790T>C | p.L597S | RefSeq | GRCh38/hg38 |
NM_001354609.1 | chr7:g.140753345_140753346delCTinsTC | c.1789_1790delCTinsTC | p.L597S | RefSeq | GRCh38/hg38 |
XM_005250045 | chr7:g.140753345_140753346delAGinsGA | c.1789_1790delCTinsTC | p.L597S | RefSeq | GRCh38/hg38 |
NM_004333.5 | chr7:g.140753345_140753346delCTinsTC | c.1789_1790delCTinsTC | p.L597S | RefSeq | GRCh38/hg38 |
NM_001378474.1 | chr7:g.140753345_140753346delCTinsTC | c.1789_1790delCTinsTC | p.L597S | RefSeq | GRCh38/hg38 |
NM_004333.6 | chr7:g.140753345_140753346delCTinsTC | c.1789_1790delCTinsTC | p.L597S | RefSeq | GRCh38/hg38 |
NM_001378473.1 | chr7:g.140749333A>G | c.1790T>C | p.L597S | RefSeq | GRCh38/hg38 |
NM_001354609.2 | chr7:g.140753345_140753346delCTinsTC | c.1789_1790delCTinsTC | p.L597S | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF R239Q BRAF L597S | melanoma | sensitive | Binimetinib + Encorafenib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mektovi (binimetinib) increased growth inhibition in patient-derived melanoma cells harboring BRAF L597S, as well as BRAF R239Q, in culture, and resulted in tumor shrinkage in 67% of tumors, increased inhibition of ERK phosphorylation, and increased tumor growth delay compared to either agent alone in a patient-derived xenograft (PDX) model (PMID: 29903896). | 29903896 |
BRAF R239Q BRAF L597S | melanoma | sensitive | Encorafenib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Braftovi (encorafenib) inhibited ERK activation and proliferation of patient-derived melanoma cells harboring BRAF L597S, as well as BRAF R239Q, in culture, and delayed tumor growth and induced shrinkage in 8% (1/12) of tumors in a melanoma patient-derived xenograft (PDX) model (PMID: 29903896). | 29903896 |
BRAF R239Q BRAF L597S | melanoma | sensitive | Binimetinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Mektovi (binimetinib) inhibited growth of patient-derived melanoma cells harboring BRAF L597S, as well as BRAF R239Q, in culture, and induced tumor shrinkage in 25% (3/12) of tumors and delayed tumor growth in a patient-derived xenograft (PDX) model (PMID: 29903896). | 29903896 |
BRAF R239Q BRAF L597S | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, the addition of Tafinlar (dabrafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a patient-derived melanoma cell line harboring BRAF L597S, as well as well as BRAF R239Q, in culture, and resulted in tumor shrinkage in 100% (13/13) of subcutaneous tumors, and decreased growth of intracranial tumors in a patient-derived xenograft (PDX) model (PMID: 29903896). | 29903896 |