Although the identification of a null ABCC8 or KCNJ11 variant(s) in an individual with CHI provides strong evidence for pathogenicity, finding a missense variant is insufficient to assign disease causality and, as such, additional support is required to achieve a “pathogenic” classification according to the guidelines set out by the American College of Medical Genetics (Richards et al., 2015). This evidence concerns the gene ABCC8 and congenital isolated hyperinsulinism.