ClinVar Miner

Submissions for variant NM_006440.5(TXNRD2):c.417del (p.Asn140fs) (rs780054798)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522567 SCV000620712 uncertain significance not provided 2017-09-08 criteria provided, single submitter clinical testing The c.417delG variant has not been published as pathogenic or been reported as benign to our knowledge. The c.417delG variant has not been observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant causes a shift in reading frame starting at codon aspartic acid 140, changing it to a threonine, and creating a premature stop codon at position 75 of the new reading frame, denoted p.Asn140ThrfsX75. This variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Nevertheless, only one other truncating variant in the TXNRD2 gene has been reported in Human Gene Mutation Database, which was reported in association with autosomal recessive familial glucocorticoid deficiency (Stenson et al., 2014). Ultimately, loss-of-function is, currently, not a well-established disease mechanism for this gene in association with either familial glucocorticoid deficiency or cardiomyopathy.
Invitae RCV001233755 SCV001406364 uncertain significance Primary dilated cardiomyopathy 2019-10-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn140Thrfs*75) in the TXNRD2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs780054798, ExAC 0.009%). This variant has not been reported in the literature in individuals with TXNRD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 451945). The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in TXNRD2 cause disease. 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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