Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000412970 | SCV000492316 | likely pathogenic | not provided | 2016-12-06 | criteria provided, single submitter | clinical testing | A novel R214P variant that is likely pathogenic has been identified in the KCNQ2 gene. The R214P variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R214P variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R214P 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 conserved position predicted to be within the Segment S4 voltage-sensor helical transmembrane domain. A different missense variant in the same residue (R214W) as well as multiple missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with KCNQ2-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |