ClinVar Miner

Submissions for variant NM_006440.5(TXNRD2):c.1406A>G (p.Asn469Ser) (rs757704344)

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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 RCV000617847 SCV000736854 uncertain significance Cardiovascular phenotype 2019-04-16 criteria provided, single submitter clinical testing The p.N469S variant (also known as c.1406A>G), located in coding exon 16 of the TXNRD2 gene, results from an A to G substitution at nucleotide position 1406. The asparagine at codon 469 is replaced by serine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to create a new alternate splice acceptor site; however, direct evidence is unavailable. 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 RCV001361064 SCV001557025 uncertain significance Primary dilated cardiomyopathy 2020-04-01 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 469 of the TXNRD2 protein (p.Asn469Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs757704344, 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: 519006). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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