Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000628861 | SCV000059462 | likely pathogenic | Hypertrophic cardiomyopathy | 2015-09-21 | criteria provided, single submitter | clinical testing | The p.Gln882Glu variant in MYH7 has been reported in 3 individuals with HCM, two of whom also carried a second likely disease-causing variant (Mohiddin 2003, Sa ntos 2012). Our laboratory has identified this variant in 1 individual with HCM and it segregated with disease in 5 affected relatives, including 2 obligate car riers. This variant was absent from large population studies. Computational pred iction tools and conservation analysis suggest that the p.Gln882Glu variant may impact the protein, though this information is not predictive enough to determin e pathogenicity. In summary, although additional studies are required to fully e stablish its clinical significance, the p.Gln882Glu variant is likely pathogenic . |
Invitae | RCV000628861 | SCV000749769 | pathogenic | Hypertrophic cardiomyopathy | 2023-10-06 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 882 of the MYH7 protein (p.Gln882Glu). This variant is present in population databases (rs397516160, gnomAD 0.007%). This missense change has been observed in individuals with hypertrophic cardiomyopathy (PMID: 12820698, 22429680, 27247418, 27532257). ClinVar contains an entry for this variant (Variation ID: 42921). 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. For these reasons, this variant has been classified as Pathogenic. |
Institute of Human Genetics, |
RCV001262905 | SCV001440951 | likely pathogenic | Dilated cardiomyopathy 1S | 2019-01-01 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics, |
RCV001723607 | SCV001950065 | likely pathogenic | Hypertrophic cardiomyopathy 1 | 2021-07-28 | criteria provided, single submitter | clinical testing | |
Gene |
RCV002286699 | SCV002577226 | likely pathogenic | not provided | 2022-09-19 | 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; This variant is associated with the following publications: (PMID: 22429680, 27247418, 27532257, 34542152, 12820698, 29300372) |