ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.2125C>A (p.Gln709Lys) (rs1554389828)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000654960 SCV000776870 uncertain significance Rasopathy 2017-12-28 criteria provided, single submitter clinical testing This sequence change replaces glutamine with lysine at codon 709 of the BRAF protein (p.Gln709Lys). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRAF-related disease. 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"). A different missense substitution at this codon (p.Gln709Arg) has been determined to be pathogenic (PMID: 19206169). This suggests that the glutamine residue is critical for BRAF protein function and that other missense substitutions at this position may also be pathogenic. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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