Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000171106 | SCV000223671 | uncertain significance | not provided | 2019-01-11 | criteria provided, single submitter | clinical testing | The Trp434Arg variant in the SNTA1 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Trp434Arg results in a non-conservative amino acid substitution of a non-polar Tryptophan with a positively charged Arginine at a position that is conserved across species. The Trp434Arg variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Nevertheless, no mutations in nearby residues have been reported in association with arrhythmia. In silico analysis predicts Trp434Arg is likely benign to the protein structure/function. With the clinical and molecular information available at this time, we cannot definitively determine if Trp434Arg is a disease-causing mutation or a rare benign variant. The pathogenic role for this variant would be further supported if it occurred de novo in an individual or if it co-segregates with an arrhythmia phenotype in a family. The variant is found in ARRHYTHMIA panel(s). |
| Invitae | RCV003765069 | SCV004619044 | uncertain significance | Long QT syndrome | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 434 of the SNTA1 protein (p.Trp434Arg). This variant is present in population databases (rs772600822, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with SNTA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 190923). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SNTA1 protein function with a negative predictive value of 80%. 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. |