The first describes a patient with a paternally inherited PMS2 PV c.2174+1G>A, which causes a splicing defect [53], and a maternally inherited POLE PV c.890C>G p.(S297C), who presented with synchronous bifocal CRC at the age of 16 years and a non-invasive high-grade urothelial carcinoma at the age of 19 years [54]. Here, POLE is linked to colorectal carcinoma.