FGFR4 and heart disorder: Several genes predicted to be intolerant by EvoTol and RVIS have been previously implicated in heart disease, including FBN2, linked to congenital contractural arachnodactyly, a disease characterized by contractions in connective tissue (40), and FGFR4 that encodes the protein Fibroblast growth factor receptor 4, a closely related gene that in mouse contains a mutation causing CHD (41).