A model to infer the pathogenic significance of CDH1 germline missense variants

摘要: Germline mutations of the E-cadherin gene (CDH1) are involved in tumorigenesis hereditary diffuse gastric cancer (HDGC). Recent studies have highlighted lifesaving potential total prophylactic gastrectomy for CDH1 germline mutation carriers. In this regard, missense type represent a clinical burden genetic counseling, as their pathogenic relevance is not straightforward. work, we outlined possible multivariate approach to infer significance such variants. We reviewed all HDGC-associated reported date. The information collected included: co-segregation within pedigrees, frequency healthy population control, recurrence independent families, and functional vitro silico data. used neighbor-joining method group according assessed robustness clusters with bootstrap test. variants were classified parameters defined analysis. This analysis allowed distribution into two distinct groups: neutral vs mutations. model described study provides an important tool that can ultimately improve counseling offered carriers