ClinVar Miner

Submissions for variant NM_000162.5(GCK):c.1361C>A (p.Ala454Glu) (rs1057524900)

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Total submissions: 1
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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 RCV000445420 SCV000537117 likely pathogenic Monogenic diabetes 2016-06-17 criteria provided, single submitter clinical testing The c.1361C>A variant in codon 454 (exon 10) of the glucokinase gene, GCK, results in the substitution of Alanine to Glutamic acid. The c.1361C>A 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) ( 16602010; 17204055; 20337973). Different amino acid substitutions at this residue, Ala454Val (14517956) and Ala454Thr (22035297), have also been reported in patients with MODY2. Additionally, multiple lines of computational evidence (SIFT, Polyphen, MutationTaster, MutationAssessor, 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, PP3

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