ClinVar Miner

Submissions for variant NM_000162.5(GCK):c.82G>A (p.Glu28Lys)

dbSNP: rs2128823215
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital RCV001526668 SCV001656298 uncertain significance Maturity onset diabetes mellitus in young 2018-04-23 criteria provided, single submitter clinical testing The c.82G>A (p.Glu28Lys) variant is predicted to substitute the glutamate at amino acid position 28 with a lysine. In silico tools have conflicting predictions as to the impact of this missense change on protein function. This alteration has not been observed by our lab and is not reported in disease databases (ClinVar) or in control populations (GnomAD). This variant has been reported in one individual with a clinical diagnosis of MODY but the clinical details of that family are limited (PMID: 19790256). Per ACMG criteria, this alteration is interpreted as a variant of uncertain clinical significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV005094714 SCV005835032 uncertain significance not provided 2024-08-10 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 28 of the GCK protein (p.Glu28Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of GCK-related conditions (PMID: 19790256, 33046911). ClinVar contains an entry for this variant (Variation ID: 1172675). 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 not expected to disrupt GCK protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of 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.