Gene Variant Detail

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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 results in impaired Braf kinase activity, but leads to activation of Erk signaling through CRAF in cell culture (PMID: 28783719), and demonstrates decreased transforming ability compared to wild-type Braf in one of two cell lines in culture (PMID: 29533785), and therefore is predicted to confer a loss of function to the Braf protein.
Associated Drug Resistance
Category Variants Paths

BRAF mutant BRAF D594X BRAF D594N

BRAF mutant BRAF inact mut BRAF D594N

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Transcript NM_004333.5
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
NM_001354609.1 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
XM_005250045 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

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  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
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  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF D594N Advanced Solid Tumor predicted - resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) did not reduce activation of Mek in transformed cells expressing BRAF D594N in culture (PMID: 28783719). 28783719
BRAF D594N lung non-small cell carcinoma predicted - sensitive RMC-4550 Preclinical - Pdx Actionable In a preclinical study, RMC-4550 treatment resulted in decreased Erk phosphorylation and dose-dependent tumor growth inhibition in patient-derived xenograft (PDX) models of non-small cell lung cancer harboring BRAF D594N (PMID: 30104724). 30104724
BRAF D594N female reproductive organ cancer no benefit Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in stable disease in a patient with gynecological cancer harboring BRAF D594N (PMID: 31924734; NCT02465060). 31924734
BRAF D594N gallbladder cancer predicted - sensitive Binimetinib + Encorafenib Case Reports/Case Series Actionable In a Phase II trial (BEAVER), Mektovi (binimetinib) and Braftovi (encorafenib) combination therapy resulted in stable disease in a patient with gallbladder cancer harboring BRAF D594N (J Clin Oncol 39, no. 15_suppl, abstr e15038; NCT03839342). detail...
BRAF D594N colorectal cancer predicted - resistant Cetuximab + Fluorouracil Case Reports/Case Series Actionable In a clinical case study, the combination of Erbitux (cetuximab) with Adrucil (fluorouracil) as a third-line therapy resulted in progressive disease in a patient with metastatic colorectal cancer harboring BRAF D594N (PMID: 31515458). 31515458
BRAF D594N colorectal cancer predicted - sensitive Irinotecan + Panitumumab Case Reports/Case Series Actionable In a clinical case study, the combination of Vectibix (panitumumab) with Camptosar (irinotecan) as a third-line therapy resulted in partial responses with 14.9 and 14.7 months progression-free survival in two patients with metastatic colorectal cancer harboring BRAF D594N (PMID: 31515458). 31515458
BRAF D594N colorectal cancer sensitive Cetuximab Preclinical - Pdx Actionable In a preclinical study, Erbitux (cetuximab) treatment inhibited tumor growth in a colorectal cancer patient-derived xenograft (PDX) model harboring BRAF D594N (PMID: 31515458). 31515458