Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000429392 | SCV000536026 | uncertain significance | not provided | 2017-01-11 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the SCN1B gene. The D83V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The D83V variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The D83V 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. This substitution occurs at a position that is conserved in mammals and in silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, missense variants in nearby residues (R85C/H and E87Q) have been reported in Human Gene Mutation Database in association with SCN1B-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |