The c.676_678del variant in the HNF1 homeobox A gene, HNF1A, is a three base pair deletion resulting in the in-frame deletion of one amino acid at codon 226 (p.(Lys226del)) within exon 3 of NM_000545.8. This variant is located within a conserved region of the DNA binding domain (codons 107-174 and 201-280) of HNF1A, which is defined as critical for the protein’s function by the ClinGen MDEP (PM1_Supporting). Additionally, this variant is absent from gnomAD v2.1.1 (PM2_Supporting). The c.676_678del variant is predicted to change the length of the protein due to an in-frame deletion of a single amino acid in a nonrepeat region (PM4_Supporting). Lastly, this variant was identified in an individual with a clinical history specific for HNF1A-MODY (MODY probability calculator result >50%, negative genetic testing for HNF4A) (PP4; internal lab contributors). In summary, c.676_678del 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 1.1, approved 9/30/21): PM1_Supporting, PM2_Supporting, PM4_Supporting, PP4.