Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002513732 | SCV000760660 | pathogenic | Catecholaminergic polymorphic ventricular tachycardia 1 | 2022-09-06 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp18Alafs*14) in the TRDN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TRDN are known to be pathogenic (PMID: 22422768, 25922419, 26200674). This variant is present in population databases (rs768049331, gnomAD 0.05%). This premature translational stop signal has been observed in individual(s) with catecholaminergic polymorphic ventricular tachycardia and long QT syndrome (PMID: 22422768, 25922419, 26768964). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is also known as p.D18fs*13. ClinVar contains an entry for this variant (Variation ID: 66015). For these reasons, this variant has been classified as Pathogenic. |
| Ai |
RCV002223180 | SCV002501141 | pathogenic | not provided | 2022-02-28 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002345363 | SCV002647194 | pathogenic | Cardiovascular phenotype | 2022-12-05 | criteria provided, single submitter | clinical testing | The c.53_56delACAG pathogenic mutation, located in coding exon 2 of the TRDN gene, results from a deletion of 4 nucleotides at nucleotide positions 53 to 56, causing a translational frameshift with a predicted alternate stop codon (p.D18Afs*14). This mutation was reported in the homozygous state in 2 unrelated individuals presenting with syncope and cardiac arrest as well as in trans with a nonsense variant in two siblings presenting with cardiac arrest (Roux-Buisson N et al. Hum. Mol. Genet., 2012 Jun;21:2759-67; Altmann HM et al. Circulation, 2015 Jun;131:2051-60; Walsh MA et al. Pacing Clin Electrophysiol, 2016 May;39:497-501). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Revvity Omics, |
RCV000056259 | SCV003820446 | pathogenic | Catecholaminergic polymorphic ventricular tachycardia 5 | 2023-02-23 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000056259 | SCV000087431 | pathogenic | Catecholaminergic polymorphic ventricular tachycardia 5 | 2012-06-15 | no assertion criteria provided | literature only |