ClinVar Miner

Submissions for variant NM_000525.4(KCNJ11):c.755T>C (p.Val252Ala)

dbSNP: rs193929352
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
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002227046 SCV002506503 benign Transitory neonatal diabetes mellitus criteria provided, single submitter research rs193929352 variant of KCNJ11 gene can cause decreased production and secretion of insulin. This can lead to MODY which is responsive to oral sulfonylureas.
Labcorp Genetics (formerly Invitae), Labcorp RCV003556057 SCV004295359 pathogenic not provided 2023-08-08 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Val252 amino acid residue in KCNJ11. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21056492, 24622368, 32893419). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects KCNJ11 function (PMID: 17021801). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KCNJ11 protein function. ClinVar contains an entry for this variant (Variation ID: 21200). This missense change has been observed in individuals with neonatal onset diabetes mellitus (PMID: 17021801, 22648966, 22815030; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 252 of the KCNJ11 protein (p.Val252Ala).
GeneReviews RCV000020357 SCV000040741 not provided Permanent neonatal diabetes mellitus no assertion provided literature only

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.