Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002526103 | SCV000637658 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2022-12-26 | criteria provided, single submitter | clinical testing | 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. 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. 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: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 463669). This variant has not been reported in the literature in individuals affected with TRDN-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.03%). This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 523 of the TRDN protein (p.Glu523Gln). This variant also falls at the last nucleotide of exon 26, which is part of the consensus splice site for this exon. |
| Ambry Genetics | RCV002404425 | SCV002709954 | uncertain significance | Cardiovascular phenotype | 2020-08-21 | criteria provided, single submitter | clinical testing | The c.1567G>C variant (also known as p.E523Q), located in coding exon 26 of the TRDN gene, results from a G to C substitution at nucleotide position 1567. The amino acid change results in glutamic acid to glutamine at codon 523, an amino acid with highly similar properties. However, this change occurs in the last base pair of coding exon 26, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is well conserved in available vertebrate species. This amino acid position is well conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |