Several single-base substitution (SBS) signatures have been described concerning POLD1-mutated tumors; SBS10c and SBS10d are linked to defective POLD1 proofreading [105], whereas SBS20 is associated with concurrent POLD1 mutations and mismatch repair deficiency [65]. Here, POLD1 is linked to hyperinsulinemic hypoglycemia, familial, 4.