ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.2644C>G (p.Gln882Glu) (rs397516160)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000628861 SCV000059462 likely pathogenic Hypertrophic cardiomyopathy 2015-09-21 criteria provided, single submitter clinical testing The p.Gln882Glu variant in MYH7 has been reported in 3 individuals with HCM, two of whom also carried a second likely disease-causing variant (Mohiddin 2003, Sa ntos 2012). Our laboratory has identified this variant in 1 individual with HCM and it segregated with disease in 5 affected relatives, including 2 obligate car riers. This variant was absent from large population studies. Computational pred iction tools and conservation analysis suggest that the p.Gln882Glu variant may impact the protein, though this information is not predictive enough to determin e pathogenicity. In summary, although additional studies are required to fully e stablish its clinical significance, the p.Gln882Glu variant is likely pathogenic .
Invitae RCV000628861 SCV000749769 pathogenic Hypertrophic cardiomyopathy 2017-11-06 criteria provided, single submitter clinical testing This sequence change replaces glutamine with glutamic acid at codon 882 of the MYH7 protein (p.Gln882Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. 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, 27247418, 27532257, 22429680). ClinVar contains an entry for this variant (Variation ID: 42921). This variant is found within a region of MYH7 between codons 181 and 937 that contains the majority of the myosin head domain. Missense variants in this region have been shown to be significantly overrepresented in individuals with hypertrophic cardiomyopathy (PMID: 27532257). 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 and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.

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