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. The gene discussed is CDH1; the disease is CDH1-related diffuse gastric and lobular breast cancer syndrome.