Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000156591 | SCV000206310 | likely pathogenic | Hypertrophic cardiomyopathy | 2014-07-01 | criteria provided, single submitter | clinical testing | The p.Ala843Thr variant in MYH7 has been identified by our laboratory as a de no vo occurrence in 1 infant with DCM. It was absent from large population studies . Alanine (Ala) at position 843 is highly conserved in evolution and the change to threonine (Thr) was predicted to be pathogenic using a computational tool cl inically validated by our laboratory. This tool's pathogenic prediction is estim ated to be correct 94% of the time (Jordan 2011). In summary, although addition al studies are required to fully establish its clinical significance, this varia nt is likely pathogenic. |
Labcorp Genetics |
RCV000156591 | SCV005773781 | uncertain significance | Hypertrophic cardiomyopathy | 2024-05-10 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 843 of the MYH7 protein (p.Ala843Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. ClinVar contains an entry for this variant (Variation ID: 179793). 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 with a positive predictive value of 95%. 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. |