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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_004333.6 | 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_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_001378473.1 | chr7:g.140749333A>G | c.1790T>C | p.L597S | RefSeq | GRCh38/hg38 |
NM_001378472.1 | chr7:g.140749333A>G | c.1790T>C | p.L597S | RefSeq | GRCh38/hg38 |
XM_005250045 | chr7:g.140753345_140753346delAGinsGA | c.1789_1790delCTinsTC | p.L597S | RefSeq | GRCh38/hg38 |
NM_001354609.1 | chr7:g.140753345_140753346delCTinsTC | c.1789_1790delCTinsTC | p.L597S | RefSeq | GRCh38/hg38 |
NM_001378468.1 | chr7:g.140753345_140753346delCTinsTC | c.1789_1790delCTinsTC | 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 L597S | melanoma | predicted - sensitive | Trametinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of melanoma cell lines harboring BRAF L597S in culture, and resulted in tumor shrinkage in 75% (8/12) subcutaneous tumors in one patient-derived xenograft (PDX) model harboring BRAF L597S that also harbored a BRAF variant of unknown significance, BRAF R239Q, however, was not sufficient to induce tumor shrinkage in a second PDX model with BRAF L597S, resulting only in tumor growth delay (PMID: 29903896). | 29903896 |
BRAF L597S | Advanced Solid Tumor | sensitive | Trametinib | Preclinical | Actionable | Preclinical studies demonstrated the MEK inhibitor, Mekinist (trametinib) caused decreased activation of MEK and ERK in cells expressing BRAF L597S (PMID: 22798288). | 22798288 |
BRAF L597S | melanoma | predicted - sensitive | Dabrafenib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Tafinlar (dabrafenib) treatment inhibited ERK activation and proliferation of melanoma cell lines harboring BRAF L597S in culture, but did not result in tumor shrinkage as a single agent in a melanoma patient-derived xenograft (PDX) model harboring BRAF L597S (PMID: 29903896). | 29903896 |
BRAF L597S | Advanced Solid Tumor | sensitive | Vemurafenib | Preclinical | Actionable | In a preclinical study, treatment of cells expressing BRAF L597S with the BRAF inhibitor, Zelboraf (vemurafenib), decreased activation of MEK and ERK (PMID: 22798288). | 22798288 |
BRAF L597S | melanoma | sensitive | Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Braftovi (encorafenib) inhibited ERK activation and proliferation of melanoma cell lines harboring BRAF L597S in culture (PMID: 29903896). | 29903896 |
BRAF L597S | melanoma | sensitive | Binimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mektovi (binimetinib) inhibited growth of melanoma cell lines harboring BRAF L597S in culture (PMID: 29903896). | 29903896 |
BRAF L597S | melanoma | predicted - sensitive | TAK-733 | Case Reports/Case Series | Actionable | In a Phase I trial, TAK-733 treatment resulted in a partial response after 2 cycles in a patient with metastatic melanoma harboring BRAF L597S, who remained progression-free for over 24 weeks (PMID: 22798288). | 22798288 |
BRAF L597S | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited growth of melanoma cell lines harboring BRAF L597S in culture (PMID: 29903896). | 29903896 |
BRAF L597S | melanoma | sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in increased growth inhibition in melanoma cell lines harboring BRAF L597S in culture, and resulted in tumor shrinkage in 89% (17/19) of tumors in a patient-derived xenograft (PDX) model harboring BRAF L597S, and treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a objective response with 34% tumor shrinkage in the patient from which the PDX model was derived from (PMID: 29903896). | 29903896 |
BRAF L597S | melanoma | sensitive | Binimetinib + Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mektovi (binimetinib) resulted in increased growth inhibition in melanoma cell lines harboring BRAF L597S in culture (PMID: 29903896). | 29903896 |
BRAF L597S | melanoma | sensitive | LY3009120 | Preclinical - Cell culture | Actionable | In a preclinical study, LY3009120 inhibited growth of melanoma cells harboring BRAF L597S in culture (PMID: 29903896). | 29903896 |
BRAF L597S | melanoma | sensitive | Encorafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in melanoma cell lines harboring BRAF L597S in culture (PMID: 29903896). | 29903896 |