ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.646C>G (p.Leu216Val)

dbSNP: rs772488436
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000492868 SCV000582658 uncertain significance not provided 2019-09-12 criteria provided, single submitter clinical testing Reported in patients with cardiomyopathy referred for genetic testing at GeneDx and in at least one individual from a cohort of patients with HCM (Waldmuller et al., 2008); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 18258667)
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV000492868 SCV000987569 likely pathogenic not provided criteria provided, single submitter clinical testing
Invitae RCV001865551 SCV002180884 uncertain significance Hypertrophic cardiomyopathy 2021-02-14 criteria provided, single submitter clinical testing This missense change is located in a region of the MYH7 protein where a significant number of previously reported MYH7 missense mutations are found (PMID: 27532257). These observations suggest that this may be a clinically significant region of the protein. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) referred for testing for hypertrophic cardiomyopathy (PMID: 18258667). ClinVar contains an entry for this variant (Variation ID: 429960). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with valine at codon 216 of the MYH7 protein (p.Leu216Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. 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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