ClinVar Miner

Submissions for variant NM_006073.4(TRDN):c.1990G>A (p.Val664Ile)

gnomAD frequency: 0.00002  dbSNP: rs756257644
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001287255 SCV001473926 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 5 2020-01-28 criteria provided, single submitter clinical testing The TRDN c.1990G>A; p.Val664Ile variant (rs756257644), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is only observed on five alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The valine at codon 664 is weakly conserved, and computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Val664Ile variant is uncertain at this time.
Labcorp Genetics (formerly Invitae), Labcorp RCV002537956 SCV001559320 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1 2022-06-08 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 664 of the TRDN protein (p.Val664Ile). This variant is present in population databases (rs756257644, gnomAD 0.004%). 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: 994234). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 RCV004035546 SCV003737748 uncertain significance Cardiovascular phenotype 2024-02-22 criteria provided, single submitter clinical testing The p.V664I variant (also known as c.1990G>A), located in coding exon 39 of the TRDN gene, results from a G to A substitution at nucleotide position 1990. The valine at codon 664 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.

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