Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV000622778 | SCV000740372 | likely pathogenic | not provided | 2016-05-18 | criteria provided, single submitter | clinical testing | |
Agnes Ginges Centre for Molecular Cardiology, |
RCV000853430 | SCV000996341 | uncertain significance | Hypertrophic cardiomyopathy | 2017-03-21 | criteria provided, single submitter | research | The MYH7 Asp1198Tyr variant is absent in the 1000 genomes project (http://www.1000genomes.org/), as well as the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/). The variant has been identified by another laboratory in a HCM proband (Genedx, pers comm.) We identified this variant in a HCM proband with a family history of disease and sudden cardiac death. The variant was found to segregate an affected sibling. Interestingly, another rare variant at this position (Arg1198Asn) have also been reported in cardiomyopathy cases, suggesting that an amino acid substitution at this site may not be tolerated. Computational tools SIFT, MutationTaster, PolyPhen-2 and PolyPhen-HCM predict this variant to have a deleterious effect. In summary, based on limited information available and rarity in the general population, we classify MYH7 Asp1198Tyr as variant of "uncertain significance". |
Invitae | RCV000853430 | SCV001406061 | uncertain significance | Hypertrophic cardiomyopathy | 2023-11-20 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 1198 of the MYH7 protein (p.Asp1198Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 28790153, 32894683). ClinVar contains an entry for this variant (Variation ID: 520451). 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. |