Description
The V399M variant in the KCNA2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The V399M variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position within the helical transmembrane domain that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in a nearby residue (P405L) has been reported in the Human Gene Mutation Database in association with epileptic encephalopathy (Stenson et al., 2014), supporting the functional importance of this region of the protein. However, the V399M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. The V399M variant is a strong candidate for a pathogenic variant, however, the possibility it may be a rare benign variant cannot be excluded.
# | Sample | Method | Observation |
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Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
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1 | germline | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |