Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002534684 | SCV000941556 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2021-02-22 | 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. 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. This variant has not been reported in the literature in individuals with TRDN-related conditions. ClinVar contains an entry for this variant (Variation ID: 647284). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 15 of the TRDN gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547). This variant occurs in the long isoform of TRDN, also known as Trisk-95 (PMID: 19403623). The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in the long isoform of TRDN cause disease. |
| Ai |
RCV002223945 | SCV002502936 | likely pathogenic | not provided | 2021-11-02 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002332631 | SCV002628922 | uncertain significance | Cardiovascular phenotype | 2019-11-19 | criteria provided, single submitter | clinical testing | The c.1166-1G>A intronic variant results from a G to A substitution one nucleotide upstream from coding exon 16 of the TRDN gene. 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, this alteration is expected to only affect the skeletal isoform of TRDN, not the predominant cardiac isoform (Kobayashi YM et al. J. Biol. Chem., 1999 Oct;274:28660-8). This nucleotide position is well conserved in available vertebrate species. Using two different splice site prediction tools, this alteration is predicted by ESEfinder to abolish the native splice acceptor site, but is not predicted to have a deleterious effect on this splice acceptor site by BDGP; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |