ClinVar Miner

Submissions for variant NM_006073.4(TRDN):c.1624+1G>A

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003075105 SCV003462597 likely pathogenic Catecholaminergic polymorphic ventricular tachycardia 1 2022-03-24 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with TRDN-related conditions. This variant is present in population databases (rs748011906, gnomAD 0.007%). This sequence change affects a donor splice site in intron 28 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), and loss-of-function variants in TRDN are known to be pathogenic (PMID: 22422768, 25922419, 26200674).
Ambry Genetics RCV003377861 SCV004097487 uncertain significance Cardiovascular phenotype 2023-09-13 criteria provided, single submitter clinical testing The c.1624+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 28 of the TRDN gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. 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.

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