Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000490202 | SCV000576671 | uncertain significance | not provided | 2017-04-21 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the SCN1B gene. The A192S variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A192S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species and in silico analysis predicts this variant likely does not alter the protein structure/function. Furthermore, the A192S variant occurs in an alternate transcript where no nearby missense variants have been reported in the Human Gene Mutation Database in association with arrhythmia (Stenson et al., 2014). |
Invitae | RCV003509547 | SCV004329410 | uncertain significance | Brugada syndrome 5 | 2023-04-23 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 426270). This variant has not been reported in the literature in individuals affected with SCN1B-related conditions. This variant is present in population databases (rs746419159, gnomAD 0.007%). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 192 of the SCN1B protein (p.Ala192Ser). |