ClinVar Miner

Submissions for variant NM_000525.4(KCNJ11):c.160C>T (p.Arg54Cys)

gnomAD frequency: 0.00001  dbSNP: rs375848765
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000516616 SCV000613862 likely pathogenic not provided 2017-12-22 criteria provided, single submitter clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002227174 SCV002506511 uncertain significance Maturity onset diabetes mellitus in young criteria provided, single submitter research Mutations in KCNJ11 gene can cause decreased production and secretion of insulin. This can lead to MODY which may be responsive to oral sulfonylureas. It is also associated with Neonatal Diabetes. However, no sufficient evidence is found to ascertain the role of this particular variant (rs375848765) in MODY yet.
Baylor Genetics RCV003464106 SCV004198068 likely pathogenic Type 2 diabetes mellitus 2023-03-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004701589 SCV005205118 uncertain significance not specified 2024-06-05 criteria provided, single submitter clinical testing Variant summary: KCNJ11 c.160C>T (p.Arg54Cys) results in a non-conservative amino acid change located in the Potassium channel, inwardly rectifying, transmembrane domain (IPR040445) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251196 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.160C>T has been reported in the literature in one homozygous individual with Congenital Hyperinsulinemia and one heterozygous individual with adult-onset diabetes; however, the clinical details of these cases were not provided (De Franco_2020). This variant has also been reported in at least two heterozygous carriers without diabetes (Billings_2022). These report(s) do not provide unequivocal conclusions about association of the variant with Congenital Hyperinsulinism or diabetes. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 447634). Based on the evidence outlined above, the variant was classified as uncertain significance.
GeneDx RCV000516616 SCV005328000 uncertain significance not provided 2023-12-14 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31291970, 32935446, 22701567, 15580558, 15718250, 31264968, 26448950, 16166157, 36208030, 32027066)

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.