Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000809848 | SCV000950028 | uncertain significance | Hypertrophic cardiomyopathy | 2021-03-13 | criteria provided, single submitter | clinical testing | 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: "Not Available"; Align-GVGD: "Class C0"). 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.Arg21 amino acid residue in TNNI3. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 16267253), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. This variant has not been reported in the literature in individuals with TNNI3-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with serine at codon 21 of the TNNI3 protein (p.Arg21Ser). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and serine. |