S1 (related to CS-1) is associated with endogenous mutational processes initiated by the spontaneous deamination of 5-methylcytosine; S2, S4, and S5 (related to CS-6 and CS-15, CS-20, and CS-21 and CS-26, respectively) are associated with dMMR and/or MSI; S3 (related to CS-3) is associated with the failure of DNA double-strand break repair by homologous recombination; S6 (related to CS-17) is of unknown etiology; and S7 (related to CS-10) is associated with error-prone polymerase activity in the catalytic subunit of DNA polymerase epsilon (POLE). Here, POLE is linked to Cowden syndrome 1.