Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000156282 | SCV000206000 | uncertain significance | not specified | 2019-03-08 | criteria provided, single submitter | clinical testing | proposed classification - variant undergoing re-assessment, contact laboratory |
CHEO Genetics Diagnostic Laboratory, |
RCV000770564 | SCV000902013 | uncertain significance | Cardiomyopathy | 2022-01-24 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001850152 | SCV002223705 | uncertain significance | Hypertrophic cardiomyopathy | 2023-07-07 | criteria provided, single submitter | clinical testing | An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. This variant disrupts the p.Asp196 amino acid residue in TNNI3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11815426, 12707239, 15607392, 26914223). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 179492). This variant has not been reported in the literature in individuals affected with TNNI3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 196 of the TNNI3 protein (p.Asp196Tyr). |