ClinVar

Description

Variant summary: KCNJ11 c.149G>A (p.Arg50Gln) results in a conservative amino acid change located in the Potassium channel, inwardly rectifying, transmembrane domain (IPR040445) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 252022 control chromosomes. c.149G>A has been reported in the literature in individuals affected with Neonatal Diabetes Mellitus and was a de-novo occurrence in a subset of these ascertained cases (example, Slingerland_2006, Shimomura_2006, Suzuki_2008, Rica_2007, Flanagan_2006, Pearson_2006, Girard_2006, Garcin_2020). It has also been reported among variants responsive to sulfonylurea treatment (example, Garcin_2020). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in reduced channel ATP sensitivity and increased sensitivity to Mg2+ upon expression of mutant homomeric and heteromeric channels in Xenopus oocytes (example, Shimomura_2006). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.