Whereas the majority of HDGC patients display CDH1 truncating mutations that induce a deleterious effect and are thus a bona fide DGC cause, around 20% harbor mutations of the missense type, which represent a major clinical challenge [20] Indeed, missense variants are difficult to assess phenotypically, thus leading to critical issues concerning genetic counseling and clinical management. This evidence concerns the gene CDH1 and Familial gastric cancer.