Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000703430 | SCV000832328 | pathogenic | Hypertrophic cardiomyopathy | 2020-11-16 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individuals with clinical features of dilated cardiomyopathy and/or left ventricular noncompaction (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 580010). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with arginine at codon 823 of the MYH7 protein (p.Gly823Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. |
Gene |
RCV003128651 | SCV003805955 | likely pathogenic | not provided | 2023-01-19 | 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; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27532257, 29300372) |
Revvity Omics, |
RCV003128651 | SCV003817662 | uncertain significance | not provided | 2019-10-21 | criteria provided, single submitter | clinical testing |