Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001707721 | SCV000620284 | likely pathogenic | not provided | 2023-06-17 | criteria provided, single submitter | clinical testing | 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; Has not been previously published as pathogenic or benign to our knowledge |
Ce |
RCV001707721 | SCV002563189 | likely pathogenic | not provided | 2022-07-01 | criteria provided, single submitter | clinical testing | MYH7: PM1, PM2, PS2:Moderate, PP2, PP4 |
Invitae | RCV002528249 | SCV003206608 | uncertain significance | Hypertrophic cardiomyopathy | 2022-06-13 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 451564). 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. 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: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. This variant is present in population databases (rs773740053, gnomAD 0.007%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 149 of the MYH7 protein (p.Glu149Lys). |
Prevention |
RCV003900092 | SCV004709223 | uncertain significance | MYH7-related condition | 2024-02-09 | criteria provided, single submitter | clinical testing | The MYH7 c.445G>A variant is predicted to result in the amino acid substitution p.Glu149Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD. This variant has been classified as a variant of uncertain significance and as likely pathogenic by different clinical submitters in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/451564/). Missense variants at a nearby residue (p.Ser148Arg, p.Ser148Ile) have been reported in individuals with hypertrophic cardiomyopathy suggesting the region may be important for protein function (Mohiddin SA et al. 2003. PubMed ID: 12820698; Khan RS et al. 2022. PubMed ID: 34935411). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |