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Gene | BRAF |
Variant | L485F |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | BRAF L485F lies within the protein kinase domain of the Braf protein (UniProt.org). L485F confers a gain of function to the Braf protein as demonstrated by increased kinase activity and activation of downstream Mek and Erk in cell culture (PMID: 16439621), increased transcription of ELK in a reporter assay (PMID: 16474404), and in one of two cell lines, L485F increased cell proliferation and cell viability compared to wild-type Braf (PMID: 29533785). |
Associated Drug Resistance | |
Category Variants Paths |
BRAF mutant BRAF act mut BRAF L485F BRAF mutant BRAF L485X BRAF L485F |
Transcript | NM_004333.6 |
gDNA | chr7:g.140778053C>A |
cDNA | c.1455G>T |
Protein | p.L485F |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001378468.1 | chr7:g.140778053C>A | c.1455G>T | p.L485F | RefSeq | GRCh38/hg38 |
XM_047420769.1 | chr7:g.140778053C>A | c.1455G>T | p.L485F | RefSeq | GRCh38/hg38 |
NM_004333 | chr7:g.140778053C>A | c.1455G>T | p.L485F | RefSeq | GRCh38/hg38 |
XM_005250045 | chr7:g.140778053C>A | c.1455G>T | p.L485F | RefSeq | GRCh38/hg38 |
NM_001354609.2 | chr7:g.140778053C>A | c.1455G>T | p.L485F | RefSeq | GRCh38/hg38 |
NM_001378474.1 | chr7:g.140778053C>A | c.1455G>T | p.L485F | RefSeq | GRCh38/hg38 |
NM_001378472.1 | chr7:g.140776995C>A | c.1455G>T | p.L485F | RefSeq | GRCh38/hg38 |
NM_004333.6 | chr7:g.140778053C>A | c.1455G>T | p.L485F | RefSeq | GRCh38/hg38 |
NM_001378473.1 | chr7:g.140776995C>A | c.1455G>T | p.L485F | RefSeq | GRCh38/hg38 |
NM_004333.5 | chr7:g.140778053C>A | c.1455G>T | p.L485F | RefSeq | GRCh38/hg38 |
NM_001354609.1 | chr7:g.140778053C>A | c.1455G>T | p.L485F | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF L485F | Advanced Solid Tumor | predicted - resistant | Dabrafenib | Preclinical - Biochemical | Actionable | In a preclinical study, cells expressing BRAF L485F were resistant to treatment with Tafinlar (dabrafenib) in culture (PMID: 34108213). | 34108213 |
BRAF L485F | Advanced Solid Tumor | predicted - resistant | Vemurafenib | Preclinical - Biochemical | Actionable | In a preclinical study, cells expressing BRAF L485F were resistant to treatment with Zelboraf (vemurafenib) in culture (PMID: 34108213). | 34108213 |
BRAF L485F | Advanced Solid Tumor | predicted - resistant | PLX8394 | Preclinical - Biochemical | Actionable | In a preclinical study, cells expressing BRAF L485F were resistant to treatment with PLX8394 in culture (PMID: 34108213). | 34108213 |
BRAF L485F | 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 6.3 months in a patient with metastatic colorectal cancer harboring BRAF L485F (PMID: 31515458). | 31515458 |
BRAF L485F | Advanced Solid Tumor | predicted - sensitive | LY3009120 | Preclinical - Biochemical | Actionable | In a preclinical study, LY3009120 treatment inhibited Erk signaling in cells expressing BRAF L485F in culture (PMID: 34108213). | 34108213 |