The c.690_691del variant in the HNF1 homeobox A gene, HNF1A, causes a frameshift in the protein at codon 230 NM_000545.8), adding 8 novel amino acids before encountering a stop codon (p.(p.Glu230AspfsTer8)). This variant, located in biologically-relevant exon 3 of 10, is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID: 23348805). This variant is absent in gnomAD v2.1.1 (PM2_Supporting), and was identified in four unrelated individuals with non- autoimmune and non-absolute/near-absolute insulin-deficient diabetes (PS4_Moderate; PMID:18003757, internal lab contributors). At least two individuals have a clinical history highly specific for HNF1A-MODY (MODY probability calculator result >50%, negative genetic testing for HNF4A, and antibody negative) (PP4_Moderate; internal lab contributor). This variant segregated with diabetes, with 3 informative meioses in a family with MODY (PP1; internal lab contributor). In summary, c.690_691del meets the criteria to be classified as pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 2.1, approved 8/11/2023): PVS1, PP4_Moderate, PS4_Moderate, PP1, PM2_Supporting.