The c.1358_*127del168insT variant in the glucokinase gene, GCK, causes a frameshift in the protein at codon 453 (NM_000162.5), adding 25 novel amino acids before encountering a stop codon (p.(S453LfsX25)). This variant, located in exon 10 of 10, is predicted to cause loss of a stop codon and result in an elongated protein. The additional residues are expected to cause improper folding, resulting in loss of function in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID 19790256). This variant is absent in gnomAD v2.1.1 (PM2_Supporting). This variant was identified in an individual with diabetes; however, PP4 could not be evaluated due to lack of clinical information (internal lab contributor). PS4_Moderate also cannot be applied because this number is below the ClinGen MDEP threshold (internal lab contributor). In summary, c.1358_*127del168insT meets the criteria to be classified as likely pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.2.0, approved 6/7/2023): PVS1, PM2_Supporting.