Worldwide, recognized genetic disorders occur in 40 to 82 per 1,000 live births.¹ The majority of patients who present to a genetic clinic, however, do not receive a molecular diagnosis despite lengthy and expensive evaluations, limiting access to appropriate counseling and support. With the advent of whole-exome sequencing (WES), all 23,000 genes can now be sequenced in a single test. Since its availability in 2011, numerous published case reports had cited benefit in patients with previously undiagnosed conditions, but the value of WES in wider clinical practice remained unknown.

To measure the diagnostic yield of WES in patients referred for evaluation of a possible genetic condition.

Consecutive case series at a single US academic center from 2011 to 2012.