High TMB was associated with periodontal disease (n = 13, 65%; p = 0.002), KMT2C mutation (n = 8, 40% vs. n = 2, 5.7%; p = 0.003), MUC16 and CASP8 mutations (n = 6, 30% each vs. n = 1, 2.9%; p = 0.007), and the presence of the ID-19 mutational signature (n = 13, 65% vs. n = 6, 17.1%; p < 0.001); conversely, and low TMB was associated with tobacco-related mutational signatures (n = 22, 62.9% vs. n = 6, 30%; p = 0.019) and the presence of the SBS 5 signature (n = 19, 54.3% vs. n = 5, 25%; p = 0.035). Here, MUC16 is linked to periodontal disorder.