ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.3634C>T (p.Arg1212Trp)

dbSNP: rs1555337102
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV000627150 SCV000747980 uncertain significance not specified 2017-03-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001055999 SCV001220417 uncertain significance Hypertrophic cardiomyopathy 2023-01-22 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYH7 protein function. ClinVar contains an entry for this variant (Variation ID: 523704). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1212 of the MYH7 protein (p.Arg1212Trp).
Agnes Ginges Centre for Molecular Cardiology, Centenary Institute RCV001089616 SCV001245092 uncertain significance Primary dilated cardiomyopathy 2018-07-11 criteria provided, single submitter research MYH7 Arg1212Trp has been previously identified in an LVNC proband (Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, MHI, ClinVar:SCV000747980.1). The variant is absent in the Genome Aggregation Database (http://gnomad.broadinstitute.org/). We identified this variant in a DCM proband and two affected relatives giving a total of 4 meiosis. Computational tools SIFT, PolyPhen-2 and MutationTaster predict this variant to be deleterious. Based on the adapted ACMG guidelines (Kelly MA, et al., 2018), this variant is rare in the general population (PM2), segregates with disease in the family (PP1) and in silico tools predict it to deleterious (PP3), therefore we classify MYH7 Arg1212Trp as a variant of 'uncertain significance'.
North West Genomic Laboratory Hub, Manchester University NHS Foundation Trust RCV005001994 SCV005627606 likely pathogenic Dilated cardiomyopathy 1S 2024-02-28 criteria provided, single submitter clinical testing PP1_Str PP3_Supp PS4_Str

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