ClinVar Miner

Submissions for variant NM_000162.5(GCK):c.748C>T (p.Arg250Cys) (rs1057524904)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Translational Genomics Laboratory,University of Maryland School of Medicine RCV000445484 SCV000537121 likely pathogenic Monogenic diabetes 2016-09-09 criteria provided, single submitter clinical testing The c.748C<T variant in codon 250 (exon 7) of the glucokinase gene, GCK, results in the substitution of Arginine to Cysteine. The c.748C<T variant was not observed in the NHLBI Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium databases; however, 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) (Milenkovic, et al. 2008, 17204055, 19790256), with evidence of co-segregation with diabetes in one family (Colclough & Ellard, personal communication). A different amino acid substitution at this residue, p.Arg250Pro, was identified in a child with incidental hyperglycemia (19564454). 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 = PS4, PM2, PP1, PP3
Athena Diagnostics Inc RCV000517148 SCV000613453 uncertain significance not specified 2017-02-06 criteria provided, single submitter clinical testing
Translational Genomics Laboratory,University of Maryland School of Medicine RCV000754803 SCV000882452 likely pathogenic Maturity-onset diabetes of the young, type 2 2017-09-21 criteria provided, single submitter clinical testing The c.748C<T variant in codon 250 (exon 7) of the glucokinase gene, GCK, results in the substitution of Arginine to Cysteine. The c.748C<T variant was not observed in the NHLBI Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium databases; however, 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) (Milenkovic, et al. 2008, 17204055, 19790256), with evidence of co-segregation with diabetes in one family (Colclough & Ellard, personal communication). A different amino acid substitution at this residue, p.Arg250Pro, was identified in a child with incidental hyperglycemia (19564454). 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 = PS4, PM2, PP1, PP3

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