Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000498527 | SCV000590134 | uncertain significance | not provided | 2017-06-01 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the SCN1B gene. The Y132X variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The Y132X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The Y132X nonsense variant in the SCN1B gene is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. However, loss of function variants in the SCN1B gene have not been reported in Human Gene Mutation Database in association with disease (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Invitae | RCV002524082 | SCV003002642 | uncertain significance | Brugada syndrome 5 | 2022-06-13 | 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: 432412). 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.Tyr132*) in the SCN1B gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 137 amino acid(s) of the SCN1B protein. |