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

gnomAD frequency: 0.00002  dbSNP: rs780054798

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000522567	SCV000620712	uncertain significance	not provided	2019-12-12	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is not a known mechanism of disease
Invitae	RCV001233755	SCV001406364	uncertain significance	Primary dilated cardiomyopathy	2023-08-23	criteria provided, single submitter	clinical testing	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. ClinVar contains an entry for this variant (Variation ID: 451945). This variant has not been reported in the literature in individuals affected with TXNRD2-related conditions. This variant is present in population databases (rs780054798, gnomAD 0.01%). 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. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in TXNRD2 cause disease.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003227778	SCV003924184	uncertain significance	Glucocorticoid deficiency 5	2021-03-30	criteria provided, single submitter	clinical testing	TXNRD2 NM_006440.4 exon5 p.Asn140Thrfs*75 (c.417delG): This variant has not been reported in the literature but is present in 0.01% (4/34526) of Latino alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/22-19905697-TC-T). This variant is present in ClinVar (Variation ID:451945). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is a deletion of one nucleotide and creates a premature stop codon 75 amino acids downstream from this location, which results in an absent or abnormal protein. However, there is insufficient evidence to establish loss of function (LOF) as a known mechanism of disease for this gene. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.