Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000189125 | SCV000242757 | likely pathogenic | not provided | 2017-03-28 | criteria provided, single submitter | clinical testing | A variant that is likely pathogenic has been identified in the SCN2A gene. The K908E variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The K908E variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The K908E 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 where amino acids with similar properties to Lysine are tolerated across species, and it is predicted to be within the pore forming loop between the S5 and S6 transmembrane segments of the second homologous domain. A missense variant in a nearby residue (K905N) has been reported in the Human Gene Mutation Database in association with an SCN2A-related disorder (Stenson et al., 2014). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Additionally, targeted parental testing indicates this variant is apparently de novo in this individual. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
| Channelopathy- |
RCV002319454 | SCV002605488 | not provided | Complex neurodevelopmental disorder | no assertion provided | literature only |