ClinVar Miner

Submissions for variant NM_000162.5(GCK):c.1148C>T (p.Ser383Leu) (rs777870079)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Kangwon National University Hospital RCV000225001 SCV000280569 likely pathogenic Maturity-onset diabetes of the young, type 2 2017-07-17 criteria provided, single submitter clinical testing Glucokinase-maturityonset diabetes of the young (GCKMODY), also known as MODY2, is caused by heterozygous inactivating mutations in the GCK gene. Because people with GCK-MODY do not develop significant microvascular complications, treatment is not recommended except pregnancy. Glucose-lowering therapy is ineffective in people with GCK-MODY.
GeneDx RCV000420976 SCV000516034 likely pathogenic not provided 2016-07-21 criteria provided, single submitter clinical testing The S383L variant has been reported in association and co-segregating with diabetes in a study of 120 patients from 73 families (Ziemssen et al., 2002), and has also been reported in several families with MODY (Barrio et al., 2002; Sujjitjoon et al., 2008). The S383L variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S383L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, this substitution occurs at a position that is not conserved. Missense variants in this residue (S383T) and in nearby residues (M381R, M381T, C382G, C382R, C382Y, A384T, A384E, G385W, G385R, G385V) have been reported in the Human Gene Mutation Database in association with hyperglycemia and MODY (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is likely pathogenic; however, the possibility it is a benign variant cannot be excluded.
Genetic Services Laboratory,University of Chicago RCV000225001 SCV000594950 likely pathogenic Maturity-onset diabetes of the young, type 2 2016-09-09 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000420976 SCV000613403 likely pathogenic not provided 2016-12-21 criteria provided, single submitter clinical testing

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