ClinVar Miner

Submissions for variant NM_006073.4(TRDN):c.1783G>A (p.Asp595Asn)

gnomAD frequency: 0.00003  dbSNP: rs771170294
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002533231 SCV000760682 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1 2022-04-25 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 595 of the TRDN protein (p.Asp595Asn). This variant also falls at the last nucleotide of exon 32, which is part of the consensus splice site for this exon. This variant is present in population databases (rs771170294, gnomAD 0.01%). 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: 532385). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV002404789 SCV002713471 uncertain significance Cardiovascular phenotype 2023-12-13 criteria provided, single submitter clinical testing The c.1783G>A variant (also known as p.D595N), located in coding exon 32 of the TRDN gene, results from a G to A substitution at nucleotide position 1783. The amino acid change results in aspartic acid to asparagine at codon 595, an amino acid with highly similar properties. However, this change occurs in the last base pair of coding exon 32, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is highly conserved in available vertebrate species. This amino acid position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. In addition, as a missense substitution, this is predicted to be tolerated by in silico analysis. 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.
Fulgent Genetics, Fulgent Genetics RCV002483825 SCV002776624 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1; Catecholaminergic polymorphic ventricular tachycardia 5 2021-09-10 criteria provided, single submitter clinical testing

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