Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000152073 | SCV000200711 | likely pathogenic | Hypertrophic cardiomyopathy | 2019-07-11 | criteria provided, single submitter | clinical testing | The p.Asp190Tyr variant in TNNI3 has been identified by our laboratory in 1 adult with HCM and segregated with disease in 4 affected relatives. It was absent from large population studies. Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. Another HCM-associated variant meeting our criteria for pathogenicity has been reported at this same position (p.Asp190Gly; Mogensen 2003) suggesting that variation at this amino acid may not be tolerated. In summary, although additional studies are required to fully establish its clinical significance, the p.Asp190Tyr variant meets criteria to be classified as likely pathogenic for autosomal dominant HCM. ACMG/AMP Criteria applied: PM2, PM5, PP1, PP3. |