Randomized prospective evaluation of genome sequencing versus standard-of-care as a first molecular diagnostic test.

Purpose: To evaluate the diagnostic yield and clinical relevance of clinical genome sequencing (cGS) as a first genetic test for patients with suspected monogenic disorders.

Methods: We conducted a prospective randomized study with pediatric and adult patients recruited from genetics clinics at Massachusetts General Hospital who were undergoing planned genetic testing. Participants were randomized into two groups: standard-of-care genetic testing (SOC) only or SOC and cGS.