Description
The I311N variant in the KCNQ2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The I311N variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The I311N 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 is predicted to be within the transmembrane segment S6 and occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. A different missense change at this residue (I311M) has been reported as pathogenic at GeneDx in association with epileptic encephalopathy. In addition, missense variants in nearby residues (A306T, A306V, A309V, G315R) 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. We interpret I311N as a likely pathogenic variant.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
