Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Translational Genomics Laboratory, |
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 |
Gene |
RCV001584122 | SCV001818879 | likely pathogenic | not provided | 2021-11-19 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate p.(A454E) has a damaging effect on protein function (imkov et al., 2017); 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 (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 17204055, 16602010, 20337973, 28842611) |