Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000154273 | SCV000203932 | likely pathogenic | Hypertrophic cardiomyopathy | 2014-04-04 | criteria provided, single submitter | clinical testing | proposed classification - variant undergoing re-assessment, contact laboratory |
Gene |
RCV000158602 | SCV000208537 | uncertain significance | not provided | 2023-09-12 | criteria provided, single submitter | clinical testing | Identified in patients with HCM referred for genetic testing at GeneDx and in published literature (Waldmuller et al., 2008; Walsh et al., 2017; Millat et al., 2010; Piras et al., 2019; Marschall et al., 2019; van Lint et al., 2019; Sepp et al., 2022; Lenarduzzi et al., 2023); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27532257, 20624503, 20800588, 31737537, 21310275, 36788754, 35626289, 30847666, 31424582, 18258667) |
Invitae | RCV000154273 | SCV001217486 | uncertain significance | Hypertrophic cardiomyopathy | 2022-09-12 | 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: 177676). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (HCM) or referred for genetic testing for HCM (PMID: 18258667, 20624503, 27532257, 30847666). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1116 of the MYH7 protein (p.Glu1116Lys). |