ClinVar Miner

Submissions for variant NM_006440.5(TXNRD2):c.1234G>A (p.Glu412Lys)

gnomAD frequency: 0.00001  dbSNP: rs781432469
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000628814 SCV000749721 uncertain significance Primary dilated cardiomyopathy 2024-01-02 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 412 of the TXNRD2 protein (p.Glu412Lys). This variant is present in population databases (rs781432469, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with TXNRD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 524925). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TXNRD2 protein function with a positive predictive value of 80%. 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.
Ambry Genetics RCV002360494 SCV002665159 uncertain significance Cardiovascular phenotype 2019-10-21 criteria provided, single submitter clinical testing The p.E412K variant (also known as c.1234G>A), located in coding exon 14 of the TXNRD2 gene, results from a G to A substitution at nucleotide position 1234. The glutamic acid at codon 412 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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