Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000221769 | SCV000272059 | uncertain significance | not specified | 2015-08-21 | criteria provided, single submitter | clinical testing | The p.Ala226Val variant in MYH7 has not been previously reported in individuals with cardiomyopathy or in large population studies. Computational prediction too ls and conservation analysis do not provide strong support for or against an imp act to the protein. In summary, the clinical significance of the p.Ala226Val var iant is uncertain. |
Invitae | RCV000232140 | SCV000284293 | pathogenic | Hypertrophic cardiomyopathy | 2023-08-16 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 228918). This missense change has been observed in individuals with hypertrophic cardiomyopathy (PMID: 27247418, 27532257; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 226 of the MYH7 protein (p.Ala226Val). 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). 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. |