Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000620353 | SCV000736787 | uncertain significance | Cardiovascular phenotype | 2023-07-01 | criteria provided, single submitter | clinical testing | The p.H430P variant (also known as c.1289A>C), located in coding exon 15 of the TXNRD2 gene, results from an A to C substitution at nucleotide position 1289. The histidine at codon 430 is replaced by proline, an amino acid with some similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001229977 | SCV001402441 | uncertain significance | Primary dilated cardiomyopathy | 2024-01-17 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 430 of the TXNRD2 protein (p.His430Pro). This variant is present in population databases (rs376463546, gnomAD 0.007%). 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: 518988). 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. |