ClinVar Miner

Submissions for variant NM_006073.4(TRDN):c.1282C>T (p.Arg428Ter)

gnomAD frequency: 0.00016  dbSNP: rs202219343
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
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.
GeneDx 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, Revvity Omics RCV001784216 SCV002020285 likely pathogenic Catecholaminergic polymorphic ventricular tachycardia 5 2022-12-21 criteria provided, single submitter clinical testing
AiLife Diagnostics, AiLife Diagnostics 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.