ClinVar

Description

c.1158_1160delinsGGG: p.Glu387Gly (E387G) in exon 5 of the CHRNA4 gene (NM_000744.5). The normal sequence with the deleted bases in braces, following immediately by the inserted bases in brackets is: TGGCC{CGA}[GGG]GCCA.The c.1158_1160delCGAinsGGG variant has not been published as a mutation nor has it been reported as a benign polymorphism, to our knowledge. This variant is not expected to result in protein truncation or nonsense-mediated mRNA decay but instead replaces a negatively charged polar Glutamic acid residue (CGA) with an uncharged non-polar Glycine residue (GGG), a change denoted as Glu387Gly (E387G). The NHLBI ESP Exome Variant Project has not identified Glu387Gly in approximately 6,500 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations.The Glu387Gly substitution alters a position that is conserved in mammals but not in related species, and it does not occur within the transmembrane region of the protein where most of the pathogenic missense mutations have been identified in association with epilepsy (Steinlein et al., 2010). In addition, in silico algorithms are not consistent in their predictions of whether Glu387Gly is damaging to the structure/function of the CHRNA4 protein. Therefore, based on the currently available information, it is unclear whether Glu387Gly is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).