Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002529900 | SCV000760607 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2024-01-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg428*) in the TRDN gene. However, it is currently unclear if variants that occur in this region of the gene cause disease. This variant is present in population databases (rs202219343, gnomAD 0.02%). 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: 532333). 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 |
RCV000760326 | SCV000890182 | uncertain significance | not provided | 2022-08-05 | criteria provided, single submitter | clinical testing | Has not been previously published in association with a TRDN-related disorder to our knowledge; Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a not a known mechanism of disease; This variant is associated with the following publications: (PMID: 31589614, 31980526) |
Revvity Omics, |
RCV001784216 | SCV002020285 | likely pathogenic | Catecholaminergic polymorphic ventricular tachycardia 5 | 2022-12-21 | criteria provided, single submitter | clinical testing | |
Ai |
RCV000760326 | SCV002502889 | likely pathogenic | not provided | 2022-02-22 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002386038 | SCV002693999 | uncertain significance | Cardiovascular phenotype | 2023-02-14 | criteria provided, single submitter | clinical testing | The p.R428* variant (also known as c.1282C>T), located in coding exon 20 of the TRDN gene, results from a C to T substitution at nucleotide position 1282. This changes the amino acid from an arginine to a stop codon within coding exon 20. This variant has been detected in the heterozygous state on exome sequencing in a case with infantile seizures and has also been detected in additional exome sequencing cohorts; however, clinical details were limited (Capalbo A et al. PLoS Genet, 2019 10;15:e1008409; Salfati EL et al. Genome Med, 2019 12;11:83; Hou YC et al. Proc Natl Acad Sci U S A, 2020 02;117:3053-3062; Park J et al. Nat Med, 2021 01;27:66-72). This alteration is expected to result in loss of function by premature protein truncation or 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. |