Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000617847 | SCV000736854 | uncertain significance | Cardiovascular phenotype | 2022-01-07 | criteria provided, single submitter | clinical testing | The p.N469S variant (also known as c.1406A>G), located in coding exon 16 of the TXNRD2 gene, results from an A to G substitution at nucleotide position 1406. The asparagine at codon 469 is replaced by serine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |
| Labcorp Genetics |
RCV001361064 | SCV001557025 | uncertain significance | Primary dilated cardiomyopathy | 2024-10-15 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 469 of the TXNRD2 protein (p.Asn469Ser). This variant is present in population databases (rs757704344, gnomAD 0.01%). 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: 519006). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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. |