ClinVar Miner

Submissions for variant NM_006440.5(TXNRD2):c.904G>A (p.Gly302Ser) (rs781228620)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519091 SCV000619605 uncertain significance not provided 2017-07-28 criteria provided, single submitter clinical testing The G302S variant of uncertain significance in the TXNRD2 gene has not beenpublished as pathogenic or been reported as benign to our knowledge. This variant is not observed at any significantfrequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome VariantServer). The G302S variant is a non-conservative amino acid substitution, which is likely to impact secondaryprotein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, in silicoanalysis predicts this variant is probably damaging to the protein structure/function. Nonetheless, this substitutionoccurs at a position that is not conserved across species and S302 is the wild type allele in at least two other species.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Invitae RCV001374084 SCV001570856 uncertain significance Primary dilated cardiomyopathy 2019-12-27 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 302 of the TXNRD2 protein (p.Gly302Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs781228620, ExAC 0.006%). This variant has not been reported in the literature in individuals with TXNRD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 450970). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.