ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.2345G>A (p.Ser782Asn) (rs886039185)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000254190 SCV000320540 likely pathogenic Cardiovascular phenotype 2015-11-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Invitae RCV000477389 SCV000546186 likely pathogenic Hypertrophic cardiomyopathy 2016-09-05 criteria provided, single submitter clinical testing This sequence change replaces serine with asparagine at codon 782 of the MYH7 protein (p.Ser782Asn). The serine residue is highly conserved and there is a small physicochemical difference between serine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with hypertrophic cardiomyopathy (PMID: 12820698, 23674513). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. A different missense substitution at this codon (p.Ser782Arg) has been determined to be pathogenic (PMID: 18533079, 23283745, 26914223, 27247418). This suggests that the serine residue is critical for MYH7 protein function and that other missense substitutions at this position may also be pathogenic. In summary, this variant is absent from population databases, has been observed in affected individuals, and affects a residue important for normal protein function. In the absence of confirmed segregation or functional evidence, at this time this variant has been classified as Likely Pathogenic.

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