Description
A variant of uncertain significance has been identified in the KCNH2 gene. The E95A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The E95A variant was not observed in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project (average read depth: 9X). The E95A 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. Additionally, this substitution occurs at a position that is conserved in mammals and in silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, likely pathogenic and pathogenic missense variants in nearby residues (E90K, E90Q, V94G) have been reported previously at GeneDx in individuals referred for LQTS genetic testing. However, segregation and functional data is necessary to fully assess the pathogenicity of this 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 |
