Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000805281 | SCV000945232 | uncertain significance | Primary dilated cardiomyopathy | 2023-05-05 | criteria provided, single submitter | clinical testing | This variant is present in population databases (no rsID available, gnomAD 0.0008%). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 485 of the TXNRD2 protein (p.Ala485Ser). This variant has not been reported in the literature in individuals affected with TXNRD2-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TXNRD2 protein function. ClinVar contains an entry for this variant (Variation ID: 650181). |