Description
The V543M variant has been previously reported in an individual with benign familial neonatal seizures; the variant was also identified in the affected father and 2 paternal aunts (Lee et al., 2017). Functional studies demonstrate the V543M variant causes a mild electrophysiological change in channel function compared to wild type (Lee et al., 2017). Missense variants in nearby residues have been reported in the Human Gene Mutation Database in individuals with with KCNQ2-related disorders (Stenson et al., 2014). The V543M variant is observed in 1/108796 (0.001%) alleles from individuals of European background (Lek et al., 2016). However, the V543M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign 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 |
