BRAF D594N

CI-VAR-00000514Explore in graph →NP_004324.2:p.Asp594AsnNM_004333.4:c.1780G>AClinVar 44813 CIViC 1107 rs397516896

Curated evidence

Evidence by cancer (10 items)

Grouped by cancer context first, then therapy. The same variant can be sensitizing in one cancer and irrelevant in another — contexts are never merged. 50 items per page; a cancer group may continue on the next page.

civicCuratedShowing 1–10 of 10 evidence items across 4 cancer contexts on this page · levels, directions and significance as curated at the source; each row links to its CIViC record.

Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Cutaneous Melanoma5
BRAF D594N	Dabrafenib	Predictive	B	Supports Sensitivity Response	—	rejected	EID2813 Patients were treated with a specific RAF inhibitor (dabrafenib), which improved overall survival of patients with BRAF mutations (P<0.003), compared to non-treated patients with BRAF mutations. Patie… (full text at CIViC) PMID 21343559 · Long et al., 2011 · Open in CIViC	civic
BRAF D594N	Dabrafenib	Predictive	D	Supports Sensitivity Response	—	rejected	EID2814 An inducible BRAF-V600E mouse melanoma model shows a tight correlation between activated BRAF and disease progression. PMID 16424035 · Hoeflich et al., 2006 · Open in CIViC	civic
BRAF D594N

ClinVar

Clinical significance (1)

ClinVar interpretations are shown as structured records — significance, review status, star rating, conditions — never flattened into one word.

clinvarCurated1 interpretation · review status and star rating as assigned by ClinVar.

Variation	Clinical significance	Review status	Stars	Conditions	Origin	Submitters	Last evaluated	Source
44813	Likely pathogenic	criteria provided, single submitter	1	Non-small cell lung carcinoma; Lung adenocarcinoma; Prostate cancer, hereditary, 1; Pilocytic astrocytoma	germline/somatic	4	May 13, 2010	clinvar

Lung Non-Small Cell Carcinoma1
BRAF D594N	Dabrafenib + TrametinibCombination	Predictive	D	Supports Sensitivity Response	2	submitted	EID8820 Non-V600 BRAF mutations occur frequently in NSCLC. While BRAF D594N results in impaired kinase activity, it can induce MEK/ERK activation when expressed in HEK293T cells in the presence of RAF1 (CRAF)… (full text at CIViC) PMID 28947956 · Noeparast et al., 2017 · Open in CIViC	civic

Malignant Neoplasm3
BRAF D594N	Vemurafenib	Predictive	D	Does Not Support Sensitivity Response	3	submitted	EID7557 RAF inhibitor vemurafenib failed to inhibit ERK signaling in tumor cells and NIH3T3 that express class 3 BRAF mutations (G466V, G466E, D594G, D594N, and G596R). PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic
BRAF D594N AND BRAF G466A	Cetuximab	Predictive	D	Does Not Support Sensitivity Response	3	submitted	EID12448 A patient with a metastatic collecting duct carcinoma of the kidney was treated with combination chemotherapy and responded except for one ovarian lesion. A PDX was generated from the ovarian lesion. … (full text at CIViC) PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic
BRAF D594N AND BRAF G466A	Capmatinib + CrizotinibSubstitutes	Predictive	D	Supports Sensitivity Response	3	submitted	EID12449 A patient with a metastatic collecting duct carcinoma of the kidney was treated with combination chemotherapy and responded except for one ovarian lesion. A PDX was generated from the ovarian lesion. … (full text at CIViC) PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic

Unmapped disease1unmapped disease
BRAF D594N	(functional)	Functional	D	Supports Gain Of Function	5	submitted	EID12985 BRAF p.Asp594Asn (NM_004333.6:c.1780G>A) causes increased MEK phosphorylation, increased ratio of pERK/ERK, increased signaling through RAF1 (CRAF), it has loss of kinase activity. Class 3 BRAF varian… (full text at CIViC) PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic