Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Diagnostics Services |
RCV001289995 | SCV001468644 | likely pathogenic | Brugada syndrome 1 | 2020-12-15 | criteria provided, single submitter | clinical testing | The c. 2777G>A variant is not present in publicly available population databases like 1000 Genomes, Exome Variant Server (EVS), Exome Aggregation Consortium (ExAC), Genome Aggregation Database (gnomAD) or in our in-house exome database. The variant lies in one of the ion transport domains [716-948aa] of the SCN5A protein. Multiple variants have been reported previously in this domain, in patients with Brugada syndrome-I. In-silico pathogenicity prediction programs have predicted this variant to be likely deleterious. |
| Invitae | RCV003770469 | SCV001531424 | uncertain significance | not provided | 2022-03-25 | 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. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 995803). This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 926 of the SCN5A protein (p.Gly926Asp). |