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Gene | BRAF |
Variant | D594N |
Impact List | missense |
Protein Effect | loss of function - predicted |
Gene Variant Descriptions | BRAF D594N lies within the protein kinase domain of the Braf protein (UniProt.org). D594N leads to activation of Erk signaling through CRAF but results in impaired Braf kinase activity in cell culture (PMID: 28783719) and decreased transformation ability compared to wild-type Braf in one of two cell lines in culture (PMID: 29533785), and therefore, is predicted to lead to a loss of Braf protein function. |
Associated Drug Resistance | |
Category Variants Paths |
BRAF mutant BRAF D594X BRAF D594N BRAF mutant BRAF inact mut BRAF D594N |
Transcript | NM_004333.6 |
gDNA | chr7:g.140753355C>T |
cDNA | c.1780G>A |
Protein | p.D594N |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_005250045 | chr7:g.140753355C>T | c.1780G>A | p.D594N | RefSeq | GRCh38/hg38 |
NM_001354609.2 | chr7:g.140753355C>T | c.1780G>A | p.D594N | RefSeq | GRCh38/hg38 |
NM_004333 | chr7:g.140753355C>T | c.1780G>A | p.D594N | RefSeq | GRCh38/hg38 |
NM_001378474.1 | chr7:g.140753355C>T | c.1780G>A | p.D594N | RefSeq | GRCh38/hg38 |
NM_004333.5 | chr7:g.140753355C>T | c.1780G>A | p.D594N | RefSeq | GRCh38/hg38 |
NM_001378468.1 | chr7:g.140753355C>T | c.1780G>A | p.D594N | RefSeq | GRCh38/hg38 |
NM_004333.6 | chr7:g.140753355C>T | c.1780G>A | p.D594N | RefSeq | GRCh38/hg38 |
NM_001354609.1 | chr7:g.140753355C>T | c.1780G>A | p.D594N | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF D594N CD274 pos NRAS Q61R | thyroid gland anaplastic carcinoma | predicted - sensitive | Dabrafenib + Sintilimab + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, combination treatment with Tafinlar (dabrafenib), Sintilimab (IBI308), and Mekinist (trametinib) resulted in a complete pathological response after two cycles allowing surgery in a patient with PD-L1 (CD274)-positive (TPS=60%, CPS=80) metastatic anaplastic thyroid carcinoma harboring BRAF D594N and NRAS Q61R, who continued on treatment with ongoing remission at 9 months after treatment initiation (PMID: 37122752). | 37122752 |