ClinVar Miner

Submissions for variant NM_000162.5(GCK):c.616A>C (p.Thr206Pro)

dbSNP: rs587780346
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory,University of Chicago RCV000117132 SCV000151293 likely pathogenic Gestational diabetes 2013-11-04 criteria provided, single submitter clinical testing
GeneDx RCV000497903 SCV000589595 pathogenic not provided 2022-10-05 criteria provided, single submitter clinical testing Described as an ethnic-specific founder variant within the Ashkenazi-Jewish population (Baldacchino et al., 2020); Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (HGMD); This variant is associated with the following publications: (PMID: 29107759, 22065275, 17937063, 22101819, 31253563, 21978167)
Athena Diagnostics Inc RCV000497903 SCV001144025 pathogenic not provided 2019-03-14 criteria provided, single submitter clinical testing Not found in the total gnomAD dataset, and the data is high quality (0/282820 chr). Statistically enriched in patients compared to ethnically matched controls. Found in at least one symptomatic patient. Predicted to have a damaging effect on the protein. One other pathogenic or likely pathogenic variant affects the same amino acid. Moderate co-segregation with disease in multiple families, but using affected individuals only.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001844042 SCV002103381 pathogenic Monogenic diabetes 2022-02-15 criteria provided, single submitter clinical testing Variant summary: GCK c.616A>C (p.Thr206Pro) results in a non-conservative amino acid change located in the Hexokinase, N-terminal domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251436 control chromosomes. c.616A>C has been reported in the literature in multiple families affected with Monogenic Diabetes (Stern_2007, Gozalan_2012, Valentinova_2012). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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.