Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000159300 | SCV000209246 | uncertain significance | not provided | 2016-07-19 | criteria provided, single submitter | clinical testing | The R158G variant has been reported previously in one Chinese proband with HCM; additional clinical information and segregation data was not provided (Zou et al., 2013). The R158G variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R158G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Furthermore, this substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, additional evidence is needed to determine whether this variant is pathogenic or benign. |
| Invitae | RCV000646065 | SCV000767822 | likely pathogenic | Hypertrophic cardiomyopathy 2; Dilated cardiomyopathy 1D; Cardiomyopathy, familial restrictive, 3 | 2023-03-23 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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 TNNT2 protein function. ClinVar contains an entry for this variant (Variation ID: 181620). This missense change has been observed in individual(s) with dilated or hypertrophic cardiomyopathy (PMID: 23283745, 31514951; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 158 of the TNNT2 protein (p.Arg158Gly). |