Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000489085 | SCV000577665 | likely pathogenic | not provided | 2015-07-28 | criteria provided, single submitter | clinical testing | The K239Q variant in the CHRNE gene has not been published as a pathogenic variant nor has it been reported as a benign polymorphism to our knowledge. The K239Q 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. The K239Q variant is a semi-conservative change at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (R238W/L, L241F) have been reported in the Human Gene Mutation Database in association with myasthenic syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein. The K239Q variant is a strong candidate for a disease-causing variant, however the possibility it may be a rare benign variant cannot be excluded |