The c.1279_1358delinsTTACA variant in the glucokinase gene, GCK, is an 80 base pair deletion/ 5 base pair insertion resulting in the in-frame deletion of 27 amino acid(s) and insertion of 2 novel amino acids between codons 427 and 453 (p.(Val427_Ser453delinsLeuGln)) within exon 10 of NM_000162.5. The c.1279_1358delinsTTACA variant is predicted to change the length of the protein due an in-frame deletion of 27 amino acids and insertion of 2 novel amino acids for a net loss of 25 amino acids in a nonrepeat region (PM4). This variant was identified in three unrelated individuals with hyperglycemia; however, PS4_Moderate cannot be applied because this number is below the ClinGen MDEP threshold (PMID: 28726111, internal lab contributors). One of these individuals had a clinical history highly specific for GCK-hyperglycemia (FBG 5.5-8 mmol/L and HbA1c 5.6 - 7.6%) (PP4; PMID:28726111). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, c.1279_1358delinsTTACA meets the criteria to be classified as a variant of uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.3.0, approved 8/11/2023): PM4, PP4, PM2_Supporting.