ClinVar Miner

Submissions for variant NM_006440.5(TXNRD2):c.1289A>C (p.His430Pro) (rs376463546)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000620353 SCV000736787 uncertain significance Cardiovascular phenotype 2017-03-27 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 2020-10-28 criteria provided, single submitter clinical testing This sequence change replaces histidine with proline at codon 430 of the TXNRD2 protein (p.His430Pro). The histidine residue is weakly conserved and there is a moderate physicochemical difference between histidine and proline. This variant is present in population databases (rs376463546, ExAC 0.01%). This variant has not been reported in the literature in individuals with TXNRD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 518988). 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.

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