Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000151288 | SCV000199220 | likely pathogenic | Primary dilated cardiomyopathy | 2015-01-29 | criteria provided, single submitter | clinical testing | The p.Met528Ile variant in MYH7 has been previously identified by our laboratory in an infant with DCM. Parental testing indicated that it likely occurred de no vo. This variant was absent from large population studies. Computational predict ion tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, although additional studies are required to fully establish its clinical significance, the p.Met528Ile variant is likely pathogenic based on its de novo occurrence. |
Invitae | RCV001204601 | SCV001375814 | uncertain significance | Hypertrophic cardiomyopathy | 2020-07-21 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with isoleucine at codon 528 of the MYH7 protein (p.Met528Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MYH7-related conditions. ClinVar contains an entry for this variant (Variation ID: 164361). 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: "Benign"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. |