ClinVar

Description

The p.R348H variant (also known as c.1043G>A), located in coding exon 1 of the KCNJ10 gene, results from a G to A substitution at nucleotide position 1043. The arginine at codon 348 is replaced by histidine, an amino acid with highly similar properties. In one study, this variant was reported in an individual with congenital hyperinsulinism of infancy (Proverbio MC et al. PLoS ONE, 2013 Jul;8:e68740). It was also detected in a child with epileptic spasms, intellectual disability, and autism as well as in her father who had severe anxiety disorder and focal abnormalities on EEG (Sicca F et al. Sci Rep, 2016 Sep;6:34325). In a child with infantile spasms, developmental delay, an abnormal EEG, left frontal lobe cortical dysplasia, hypotonia, and brachycephaly, this variant co-occurred with an apparently de novo SCN8A pathogenic mutation (Butler KM et al. Epilepsy Res., 2017 01;129:17-25). Of note, none of the four aforementioned individuals were found to carry a second KCNJ10 alteration. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on available evidence to date, the clinical significance of this alteration remains unclear.