Hereditary diffuse gastric cancer is an inherited cancer predisposition syndrome associated with CDH1 germline mutations. To date, more than 500 mutations are described from different countries, with a particular higher mutation frequency in countries with low incidence for gastric cancer. The distribution of germline mutations sub-types in this inherited cancer susceptibility is rather heterogeneous: missense variants represent about 23.3% of the cases, followed by deletions (22.6%) and non-sense (22.2%), and splicing alterations (21.5%). Insertions are less frequently described, constituting 10.3% of all CDH1 mutations. If we consider CDH1 germline mutations identified in healthy individuals respecting to subjects affected by gastric tumor, we observed a higher frequency of splicing and missense mutations in healthy individuals rather than gastric cancer patients, and these mutations seem to be associated with a lower risk for developing gastric cancer. (By Dr. Giovanni Corso, https://jmg.bmj.com/content/early/2021/12/23/jmedgenet-2021-108226 )