ClinVar Miner

Submissions for variant NM_006073.4(TRDN):c.2084A>T (p.Asp695Val)

gnomAD frequency: 0.00006  dbSNP: rs202040879
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002526418 SCV000548540 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1 2022-07-17 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 695 of the TRDN protein (p.Asp695Val). This variant is present in population databases (rs202040879, 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: 408739). 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: "Probably Damaging"; Align-GVGD: "Class C0"). 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 RCV000493942 SCV000582006 uncertain significance not provided 2017-05-05 criteria provided, single submitter clinical testing The D695V variant of uncertain significance in the TRDN gene has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The D695V variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Ambry Genetics RCV002418386 SCV002727103 uncertain significance Cardiovascular phenotype 2022-05-03 criteria provided, single submitter clinical testing The p.D695V variant (also known as c.2084A>T), located in coding exon 41 of the TRDN gene, results from an A to T substitution at nucleotide position 2084. The aspartic acid at codon 695 is replaced by valine, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002489049 SCV002775095 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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