Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000421894 | SCV000535636 | uncertain significance | not specified | 2017-01-03 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the TXNRD2 gene. The R254C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R254C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In addition, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Data from control individuals was not available to assess whether R254C may be a common benign variant in the NHLBI Exome Sequencing Project. However, the Exome Aggregation Consortium (ExAC) reports this variant has been observed at a low frequency (0.6%; 3/496 alleles) in individuals of Latino background.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. This result cannot be interpreted for diagnosis or used for family member screening at this time. |
| Knight Diagnostic Laboratories, |
RCV001270087 | SCV001448898 | uncertain significance | Glucocorticoid deficiency 5 | 2019-04-19 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001851085 | SCV002227637 | uncertain significance | Primary dilated cardiomyopathy | 2024-11-26 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 254 of the TXNRD2 protein (p.Arg254Cys). This variant is present in population databases (rs183950022, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. 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: 392373). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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 | RCV002393059 | SCV002673753 | likely benign | Cardiovascular phenotype | 2018-03-21 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Fulgent Genetics, |
RCV001270087 | SCV002782340 | uncertain significance | Glucocorticoid deficiency 5 | 2021-09-09 | criteria provided, single submitter | clinical testing |