Of interest, two of these patients (age at biopsy 19 and 33) most likely have constitutional mismatch repair deficiency syndrome, since they each harbored two PGVs in PMS2 and both were microsatellite instable with a high tumor mutational burden, without somatic driver mutations in any one of the four MMR genes (Table 1, Fig. 1). Here, MRC1 is linked to neoplasm.