Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001061114 | SCV001225846 | pathogenic | Brugada syndrome 5 | 2025-01-09 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 2 of the SCN1B gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN1B-related conditions. ClinVar contains an entry for this variant (Variation ID: 855779). 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. This variant disrupts a region of the SCN1B protein in which other variant(s) (p.Trp179*) have been determined to be pathogenic (PMID: 18464934; internal data). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |