Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001054192 | SCV001218495 | uncertain significance | Primary dilated cardiomyopathy | 2019-02-14 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 7 of the TXNRD2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TXNRD2-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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. |
| Ambry Genetics | RCV003346285 | SCV004058557 | uncertain significance | Cardiovascular phenotype | 2023-06-27 | criteria provided, single submitter | clinical testing | The c.591+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 7 of the TXNRD2 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. However, the evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |