ClinVar

Description

p.His443Asp (CAC>GAC): c.1327 C>G in exon 5 of the CHRNA4 gene (NM_000744.5)The His443Asp missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,200 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 variant is a non-conservative amino acid substitution of a positively charged Histidine residue with a negatively charged Aspartic acid residue. However, His443Asp alters a poorly conserved position in the topological domain of the CHRNA4 protein and in silico analysis predicts this variant likely has a benign effect on the protein structure/function. In addition, the His443Asp amino acid substitution does not occur within the transmembrane region of the protein where most pathogenic missense mutations have been identified in association with epilepsy (Steinlein et al., 2010). Therefore, based on the currently available information, it is unclear whether His443Asp is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).