Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000578998 | SCV000680863 | uncertain significance | not provided | 2017-08-07 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the SCN1B gene. The E66X variant hasnot been published as a pathogenic variant, nor has it been reported as a benign variant to ourknowledge. It was not observed in approximately 6,500 individuals of European and AfricanAmerican ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benignvariant in these populations. The E66X nonsense variant is predicted to cause loss of normalprotein function either through protein truncation or nonsense-mediated mRNA decay. However,nonsense variants have not been reported in the Human Gene Mutation Database in associationwith SCN1B-related disorders (Stenson et al., 2014). Therefore, based on the currently availableinformation, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Invitae | RCV001368794 | SCV001565205 | uncertain significance | Brugada syndrome 5 | 2023-01-06 | 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 488917). This variant has not been reported in the literature in individuals affected with SCN1B-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu66*) in the SCN1B gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 203 amino acid(s) of the SCN1B protein. |