The study and characterization of structural and dynamical features of protein-protein interactions is of paramount importance in our understanding of cellular mechanisms and the emergence of pathology. Patterns of coordinated mutations that determine changes at protein contacts characterize the co-evolution of interacting proteins. The identification of those mutations allow the systematic prediction of protein contacts and the study of the interplay between co-evolution and structural conservation with a special focus on mutation pathogenicity of specific protein families. Such computational methods devoted to the interpretation of protein variants will expand our knowledge on the mechanisms by which mutations contribute to diseases, including cancer