ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.2893G>A (p.Glu965Lys) (rs863225100)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory of Genetics and Molecular Cardiology, University of São Paulo RCV000201512 SCV000256136 likely pathogenic Familial hypertrophic cardiomyopathy 1 criteria provided, single submitter clinical testing
GeneDx RCV000494219 SCV000581926 likely pathogenic not provided 2015-08-06 criteria provided, single submitter clinical testing The E965K has been identified in two individuals with HCM and was absent from at least 300 control alleles (Olivotto et al., 2008; Marsiglia et al., 2013). The E965K variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Additionally, the E965K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, missense variants in nearby residues (D955N, L961R) have been reported in the Human Gene Mutation Database in association with cardiomyopathy (Stenson et al., 2014), supporting the functional importance of this region of the protein.Therefore, this variant is a strong candidate for a pathogenic variant however the possibility that it is a benign variant cannot be excluded.

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