Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001842182 | SCV002053337 | uncertain significance | Cardiac arrhythmia | 2021-07-07 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 28 of the SCN5A gene, creating a premature translation stop signal in the last exon. This variant is expected to result in the expression of a truncated protein lacking the last 28 amino acids of the SCN5A protein. To our knowledge, this variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Gene |
RCV003320847 | SCV004025544 | uncertain significance | not provided | 2023-08-11 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation as the last 28 amino acids are lost, although loss-of-function variants have not been reported downstream of this position in the protein; Has not been previously published as pathogenic or benign to our knowledge |
| Laboratory for Molecular Medicine, |
RCV003320847 | SCV004848068 | uncertain significance | not provided | 2017-07-17 | criteria provided, single submitter | clinical testing | The p.Gln1989X variant in SCN5A has not been previously reported in individuals with SCN5A-associated channelopathies or in large population studies. This nonsense variant leads to a premature termination codon at position 1989. This alteration occurs within the last exon and is more likely to escape nonsense mediated decay (NMD) and therefore result in a truncated protein. While loss-of-function variants in SCN5A are considered to be disease-causing for Brugada syndrome/DCM, variants affecting protein length are more prevalent in the last exon of individuals in the ostensibly healthy population where this variant is located (see ExAC). In summary, while there is some suspicion for a pathogenic role, the clinical significance of the p.Gln1989X variant is uncertain. |