ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.737A>G (p.Lys246Arg)

gnomAD frequency: 0.00003  dbSNP: rs730880851
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158759 SCV000208694 likely pathogenic not provided 2022-06-21 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27532257, 29300372)
Invitae RCV000802891 SCV000942740 uncertain significance Hypertrophic cardiomyopathy 2021-10-21 criteria provided, single submitter clinical testing 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). 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. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 181321). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with arginine at codon 246 of the MYH7 protein (p.Lys246Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV003486716 SCV004239496 uncertain significance Cardiomyopathy 2023-01-05 criteria provided, single submitter clinical testing

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