Description
A novel M211V variant that is likely pathogenic has been identified in the KCNQ2 gene. The M211V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The M211V variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution alters a conserved position predicted to be within the transmembrane segment S4 voltage sensor domain (Richards et al., 2004). 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. Additionally, in silico analysis predicts this variant is probably damaging to the protein structure/function. However, the M211V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
| # | 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 |
