ClinVar Miner

Submissions for variant NM_006440.5(TXNRD2):c.1001C>T (p.Thr334Ile)

gnomAD frequency: 0.00004  dbSNP: rs780014083
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001786911 SCV002028903 uncertain significance not provided 2024-04-25 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function
Ambry Genetics RCV002386564 SCV002690938 uncertain significance Cardiovascular phenotype 2020-12-09 criteria provided, single submitter clinical testing The p.T334I variant (also known as c.1001C>T), located in coding exon 12 of the TXNRD2 gene, results from a C to T substitution at nucleotide position 1001. The threonine at codon 334 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and isoleucine is the reference amino acid in other 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002541252 SCV003480634 uncertain significance Primary dilated cardiomyopathy 2024-01-31 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 334 of the TXNRD2 protein (p.Thr334Ile). This variant is present in population databases (rs780014083, gnomAD 0.03%). 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: 1326731). 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 not expected to disrupt TXNRD2 protein function with a negative 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.

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