Submissions for variant NM_000525.4(KCNJ11):c.697C>T (p.Leu233Phe)

dbSNP: rs1564865302

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Translational Genomics Laboratory, University of Maryland School of Medicine	RCV000754813	SCV000882463	likely pathogenic	Maturity-onset diabetes of the young type 13	2018-02-09	criteria provided, single submitter	clinical testing	The c.697C>T variant in codon 233 (exon 1 of the RefSeqGene) of the potassium voltage-gated channel subfamily J member 11gene, KCNJ11, results in the substitution of Leucine to Phenylalanine. Mutations in KCNJ11 have been reported in patients with permanent neonatal diabetes (PNDM) with or without developmental delay and epilepsy, transient neonatal diabetes (TNDM), and maturity-onset diabetes of the young, type 13 (MODY13) (21054355, 22701567). The c.697C>T variant was not observed in the NHLBI Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium databases; however, the c.697C>T variant was previously identified in a five-week old boy who presented with diabetic ketoacidosis and was successfully treated with oral glibenclamide (21210267). Additionally, multiple lines of computational evidence (LRT, MutationTaster, FATHMM, MetaSVM, MetalR, Provean, GERP, CADD) predict this variant is probably damaging to the protein structure, function, or protein-protein interaction. The p.Leu233Phe variant was shown to be sensitive to sulfonylurea using an in vitro tolbutamide assay (27033559). ACMG criteria = PS3, PM2, PP3