ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.785A>G (p.Gln262Arg) (rs397516904)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Greenwood Genetic Center Diagnostic Laboratories,Greenwood Genetic Center RCV000157699 SCV000207685 likely pathogenic not provided 2015-01-15 no assertion criteria provided clinical testing
Invitae RCV000205969 SCV000259868 likely pathogenic Rasopathy 2015-08-08 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 262 of the BRAF protein (p.Gln262Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is not present in population databases and has been reported in the literature. ClinVar also contains an entry for this variant (RCV000157699). This variant was reported in an individual affected with cardio-facio-cutaneous syndrome (PMID: 17704260) and in an individual affected with Noonan syndrome (PMID: 19953625). Full parental testing was not performed in either cases, but were suspected to be sporadic. Two other missense substitutions at this codon (p.Gln262Lys and p.Gln262Pro) have been reported as de novo mutations in patients affected with cardio-facio-cutaenous syndrome (PMID: 18042262, 25463315). This suggests that the glutamine residue is important for BRAF protein function. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Likely Pathogenic.

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