NOD2 and Cowden disease: The strongest genetic association for CD susceptibility is in the gene encoding the nucleotide-binding oligomerisation domain-containing protein 2 [NOD2; also known as CARD15].20,21 The three most common CD-associated NOD2 mutations, R702W and G908R, result in amino acid substitutions and L1007fsinsC results in a premature stop codon and dysfunctional NOD2.