An association between pheochromocytoma expression and amino acid substitutions at codon 618 was observed as follows: 0 of 7 patients with C618F, 5 of 21 patients with C618G (24%), 11 of 27 patients with C618R (41%), 7 of 41 patients with C618S (17%), and 0 of 9 patients with C618Y (P = .04.)
The novel variants K666E, IVS9-11G-->A, D631V in cis with H665Q, D631E (with C634Y), E623K (in trans with C618S), 616delGAG (in trans with C609Y), Y606C, C630R, and R635-T636insELCR;T636P were detected in patients with various clinical presentations ranging from thyroid goiter, medullary thyroid carcinoma, and pheochromocytoma to classic multiple endocrine neoplasia type 2A.