Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000245936 | SCV000320630 | uncertain significance | Cardiovascular phenotype | 2021-06-17 | criteria provided, single submitter | clinical testing | The p.V505D variant (also known as c.1514T>A), located in coding exon 17 of the TXNRD2 gene, results from a T to A substitution at nucleotide position 1514. The valine at codon 505 is replaced by aspartic acid, an amino acid with highly dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV001854998 | SCV002244035 | uncertain significance | Primary dilated cardiomyopathy | 2024-01-17 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 505 of the TXNRD2 protein (p.Val505Asp). This variant is present in population databases (rs759613137, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with TXNRD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 264602). 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 not expected to disrupt TXNRD2 protein function with a negative predictive value of 80%. 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. |