ClinVar

Description

The KCNE2 c.79C>T; p.Arg27Cys variant (rs74315449, ClinVar variant ID 6055) was detected in two Chinese patients with atrial fibrillation (Yang 2004) and was also one of two KCNE2 variants present in a child with long QT syndrome (Sauer 2016). Relatives of the Chinese patients who also carried the variant had mild cardiac symptoms, making it unclear whether or not the variant segregated with disease in these families (Yang 2004). Functional studies of this variant in cell lines were consistent with it being a gain-of-function variant; other gain-of-function variants in KCNE2 are associated with atrial fibrillation and short QT syndrome, while loss-of-function variants are more often associated with long QT syndrome (Yang 2004, Liu 2014). This variant is listed in the genome Aggregation Database (gnomAD) with an overall population frequency of 0.01% (identified on 37 out of 277,220 chromosomes). The arginine at position 27 is highly conserved, considering 11 species, and computational analyses of the effects of the p.Arg27Cys variant on protein structure and function predict a deleterious effect (SIFT: damaging, PolyPhen-2: probably damaging). Based on the available information, the clinical significance of the p.Arg27Cys variant cannot be determined with certainty.