ClinVar Miner

Submissions for variant NM_006440.5(TXNRD2):c.259G>A (p.Val87Ile) (rs201658653)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498114 SCV000589933 uncertain significance not provided 2017-06-29 criteria provided, single submitter clinical testing The V87I variant in the TXNRD2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The V87I variant is not observed in the homozygous state or at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The V87I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret V87I as a variant of uncertain significance.
Invitae RCV000793287 SCV000932635 uncertain significance Primary dilated cardiomyopathy 2020-10-16 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 87 of the TXNRD2 protein (p.Val87Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs201658653, ExAC 0.02%). This variant has not been reported in the literature in individuals with TXNRD2-related disease. ClinVar contains an entry for this variant (Variation ID: 432228). 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. 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.

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