ClinVar Miner

Submissions for variant NM_002471.3(MYH6):c.3893C>T (p.Ala1298Val) (rs368588052)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000157338 SCV000207075 likely benign Primary familial hypertrophic cardiomyopathy 2014-10-06 no assertion criteria provided clinical testing
Invitae RCV000463802 SCV000546144 uncertain significance Familial hypertrophic cardiomyopathy 14 2017-05-02 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 1298 of the MYH6 protein (p.Ala1298Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs368588052, ExAC 0.1%) but has not been reported in the literature in individuals with a MYH6-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: "Possibly Damaging"; Align-GVGD: "Class C0"). However, algorithms developed to predict the effect of sequence changes on mRNA splicing suggest that this variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a rare missense change with uncertain impact on protein function and splicing. It is not expected to cause disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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