ClinVar Miner

Submissions for variant NM_000525.4(KCNJ11):c.353C>T (p.Ser118Leu)

gnomAD frequency: 0.00002  dbSNP: rs756424776
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV001822199 SCV002069714 uncertain significance not specified 2018-02-19 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002489866 SCV002775268 uncertain significance Diabetes mellitus, transient neonatal, 3; Hyperinsulinemic hypoglycemia, familial, 2; Type 2 diabetes mellitus; Maturity-onset diabetes of the young type 13; Diabetes mellitus, permanent neonatal 2 2022-01-18 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001822199 SCV005887508 uncertain significance not specified 2025-01-24 criteria provided, single submitter clinical testing Variant summary: KCNJ11 c.353C>T (p.Ser118Leu) results in a non-conservative amino acid change located in the inward rectifier potassium channel 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 allele was found at a frequency of 2.4e-05 in 251194 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.353C>T has been reported in the literature in individuals affected with diabetes or with a family history of diabetes/hyperinsulinism (e.g., Boodram_2011, DeFranco_2020, Donath_2019, Vedovato_2024). These reports do not provide unequivocal conclusions about association of the variant with Congenital Hyperinsulinism. At least one publication reports experimental evidence evaluating an impact on protein function (Vedovato_2024). The most pronounced variant effect results in 60% of normal cell surface expression compared to wild type. The following publications have been ascertained in the context of this evaluation (PMID: 22512215, 32027066, 31291970, 38366195). ClinVar contains an entry for this variant (Variation ID: 1336017). Based on the evidence outlined above, the variant was classified as uncertain significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.