BRAF L525R
Gene Variant Detail

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Gene BRAF
Variant L525R
Impact List missense
Protein Effect gain of function - predicted
Gene Variant Descriptions BRAF L525R lies within the protein kinase domain of the Braf protein (UniProt.org). L525R results in increased activation of Erk signaling in a dimer-dependent but RAS-independent manner (PMID: 31515458, PMID: 28972961), 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 L525R

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Transcript NM_004333.6
gDNA chr7:g.140777032A>C
cDNA c.1574T>G
Protein p.L525R
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_001354609.1 chr7:g.140777032A>C c.1574T>G p.L525R RefSeq GRCh38/hg38
XM_017012559.1 chr7:g.140778054_140778055delTTinsAG c.1573_1574delTTinsAG p.L525R RefSeq GRCh38/hg38
NM_001374244.1 chr7:g.140778054_140778055delTTinsAG c.1573_1574delTTinsAG p.L525R RefSeq GRCh38/hg38
XM_047420767.1 chr7:g.140778054_140778055delTTinsAG c.1573_1574delTTinsAG p.L525R RefSeq GRCh38/hg38
NM_004333.6 chr7:g.140777032A>C c.1574T>G p.L525R RefSeq GRCh38/hg38
NM_001378468.1 chr7:g.140777032A>C c.1574T>G p.L525R RefSeq GRCh38/hg38
NM_001374258.1 chr7:g.140778054_140778055delTTinsAG c.1573_1574delTTinsAG p.L525R RefSeq GRCh38/hg38
XM_047420769.1 chr7:g.140777032A>C c.1574T>G p.L525R RefSeq GRCh38/hg38
XM_017012558.1 chr7:g.140778054_140778055delTTinsAG c.1573_1574delTTinsAG p.L525R RefSeq GRCh38/hg38
XM_047420768.1 chr7:g.140778054_140778055delTTinsAG c.1573_1574delTTinsAG p.L525R RefSeq GRCh38/hg38
NM_001354609.2 chr7:g.140777032A>C c.1574T>G p.L525R RefSeq GRCh38/hg38
NM_004333.5 chr7:g.140777032A>C c.1574T>G p.L525R RefSeq GRCh38/hg38
XM_017012559.2 chr7:g.140778054_140778055delTTinsAG c.1573_1574delTTinsAG p.L525R RefSeq GRCh38/hg38
XM_047420766.1 chr7:g.140776996_140776997delTTinsAG c.1573_1574delTTinsAG p.L525R RefSeq GRCh38/hg38
NM_001378474.1 chr7:g.140777032A>C c.1574T>G p.L525R RefSeq GRCh38/hg38
NM_001378472.1 chr7:g.140754198A>C c.1574T>G p.L525R RefSeq GRCh38/hg38
NM_001378475.1 chr7:g.140753297_140753298delTTinsAG c.1573_1574delTTinsAG p.L525R RefSeq GRCh38/hg38
NM_001378473.1 chr7:g.140754198A>C c.1574T>G p.L525R RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF L525R colorectal cancer not predictive Cetuximab Case Reports/Case Series Actionable In a clinical study, Erbitux (cetuximab) treatment as a third-line therapy resulted in stable disease with progression-free survival of 4 months in a patient with metastatic colorectal cancer harboring BRAF L525R (PMID: 31515458). 31515458
BRAF L525R Advanced Solid Tumor sensitive Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Koselugo (selumetinib) inhibited viability of cells expressing BRAF L525R in culture (PMID: 36856908). 36856908
BRAF L525R Advanced Solid Tumor predicted - sensitive Dactolisib + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the addition of Dactolisib (BEZ235) to treatment with Koselugo (selumetinib) resulted in increased inhibition of proliferation in Koselugo (selumetinib)-resistant cells expressing BRAF L525R compared to Dactolisib (BEZ235) alone (PMID: 36856908). 36856908
BRAF L525R Advanced Solid Tumor sensitive Dactolisib Preclinical - Cell culture Actionable In a preclinical study, Dactolisib (BEZ235) inhibited viability of cells expressing BRAF L525R in culture (PMID: 36856908). 36856908