Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001361098 | SCV001557062 | uncertain significance | Primary dilated cardiomyopathy | 2020-02-12 | criteria provided, single submitter | clinical testing | 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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with TXNRD2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with aspartic acid at codon 200 of the TXNRD2 protein (p.Gly200Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. |
Gene |
RCV001776220 | SCV002012626 | uncertain significance | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function |
Ambry Genetics | RCV002357224 | SCV002658788 | uncertain significance | Cardiovascular phenotype | 2023-06-19 | criteria provided, single submitter | clinical testing | The p.G200D variant (also known as c.599G>A), located in coding exon 8 of the TXNRD2 gene, results from a G to A substitution at nucleotide position 599. The glycine at codon 200 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is highly 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. |