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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