Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000558828 | SCV000623488 | uncertain significance | Primary dilated cardiomyopathy | 2017-03-05 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with proline at codon 479 of the TXNRD2 protein (p.Leu479Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs756559860, ExAC 0.003%) but has not been reported in the literature in individuals with a TXNRD2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV003159713 | SCV003853899 | uncertain significance | Cardiovascular phenotype | 2023-02-21 | criteria provided, single submitter | clinical testing | The p.L479P variant (also known as c.1436T>C), located in coding exon 16 of the TXNRD2 gene, results from a T to C substitution at nucleotide position 1436. The leucine at codon 479 is replaced by proline, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |