Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000158890 | SCV000208825 | likely pathogenic | not provided | 2022-07-26 | criteria provided, single submitter | clinical testing | Segregates with disease in affected individuals from several unrelated families referred for genetic testing at GeneDx and in the published literature (Agarwal et al., 2015); 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: 29121657, 27532257, 29300372, 33407484, 33658040, 26271555) |
Invitae | RCV000792651 | SCV000931960 | likely pathogenic | Hypertrophic cardiomyopathy | 2022-07-03 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 181409). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 539 of the MYH7 protein (p.Met539Val). This missense change has been observed in individuals with hypertrophic cardiomyopathy (PMID: 26271555, 29121657, 33407484, 33658040; Invitae). This variant is not present in population databases (gnomAD no frequency). |