ClinVar Miner

Submissions for variant NM_000162.5(GCK):c.128G>A (p.Arg43His) (rs764232985)

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
Translational Genomics Laboratory,University of Maryland School of Medicine RCV000445457 SCV000537123 likely pathogenic Monogenic diabetes 2016-07-22 criteria provided, single submitter clinical testing The c.128G>A variant in codon 43 (exon 2) of the glucokinase gene, GCK, results in the substitution of Arginine to Histidine. This variant has been reported in the literature in patients with a clinical picture consistent with Maturity-Onset Diabetes of the Young, Type 2 (MODY2, also called GCK-MODY) (22611063, 22493702, 11942313), with evidence of co-segregation with diabetes in two separate families (22611063, 22493702). Different amino acid substitutions at this residue, Arg43Ser and Arg43Cys, have also been reported in patients with MODY2 (17573900, 19358091, 25015100). Functional studies suggest that the Arg43His and Arg43Cys substitutions result proteins with decreased stability compared to wild-type (22611063, 25015100). Additionally, multiple lines of computational evidence (SIFT, Polyphen, MutationTaster, LRT, FATHMM, SVM, LR, CADD, GERP) predict this variant is probably damaging to the protein structure, function, or protein-protein interaction. ACMG Criteria = PS3, PP1, PP3
Athena Diagnostics Inc RCV000711763 SCV000842157 likely pathogenic not provided 2017-12-21 criteria provided, single submitter clinical testing

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.