Description
The E82K mutation was reported to segregate with DCM and atrial ventricular block in eight individuals from two Chinese families (Wang et al., 2006; Wu et al., 2010). E82K was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In vitro studies showed E82K significantly reduced expression and altered localization of connexin 43 (Sun et al., 2010). Studies in transgenic mice showed E82K activates the FAS and mitochondrial pathways of apoptosis in heart tissue (Lu et al., 2010). E82K 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 occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense mutations in nearby residues (R72L, R72C, L85R, R89L) have been reported in the Human Gene Mutation Database in association with cardiomyopathy (Stenson et al., 2014), supporting the functional importance of this region of the protein.
| # | 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 |
