A recent study showed that hypermutant cancers were enriched for defects in mismatch repair pathway genes POLE and POLD1. 65 Different POLE germline mutations could result in different mutation burdens in tumors and that not all tumors with POLE mutations were associated with hypermutation; drive mutations of POLE were uncovered outside the exonuclease domain, indicating that other domains may be responsible for proof reading.65 In our study, only two of eight solitary germline mutations were located in the exonuclease domain. Here, POLD1 is linked to cancer.