Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000490238 | SCV000576691 | likely pathogenic | not provided | 2017-04-21 | criteria provided, single submitter | clinical testing | The F1619S variant in the SCN2A gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The F1619S variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The F1619S 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 across species and is located within the extracellular loop between S3 and S4 transmembrane segments of the fourth homologous domain. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret F1619S as a likely pathogenic variant. |