Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002523314 | SCV000548528 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2022-08-19 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 25 of the TRDN gene. It does not directly change the encoded amino acid sequence of the TRDN protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs189125299, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with TRDN-related conditions. ClinVar contains an entry for this variant (Variation ID: 408727). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
Gene |
RCV000497346 | SCV000590699 | uncertain significance | not provided | 2021-05-26 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV000618646 | SCV000737653 | uncertain significance | Cardiovascular phenotype | 2023-08-15 | criteria provided, single submitter | clinical testing | The c.1537+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 25 of the TRDN gene. This nucleotide position is well 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, this alteration does not impact the predominant cardiac isoform of TRDN (NM_001256021.1; Kobayashi YM et al. J. Biol. Chem., 1999 Oct;274:28660-8). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Ai |
RCV000497346 | SCV002501753 | uncertain significance | not provided | 2021-07-22 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002506123 | SCV002815545 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1; Catecholaminergic polymorphic ventricular tachycardia 5 | 2022-04-04 | criteria provided, single submitter | clinical testing |