Reanalysis of clinical exome data at a two- to three-year interval could result in an incremental 10 percent diagnostic yield, according to a study published online July 21 in Genetics in Medicine. The authors offer some practical suggestions for laboratories evaluating the cost-benefit of the time, labor, and expense associated with reanalysis versus the incremental gain in understanding of variant-disease associations reported each year. A 25 percent diagnostic yield for clinical exome sequencing of patients with presumed Mendelian disorders has been previously reported. However, approximately 250 new, gene-disease and 9,200 variant-disease associations are reported annually, the authors say. In the present study raw exome (pro-band only) and phenotypic data of 40 individuals with previously nondiagnostic clinical exomes were reanalyzed with current software (ANNOVAR, version 527, to annotate variants) and literature for each candidate causative variant. Overall, the majority of participants were female (n=25), 10 years of age or younger at the time of initial sample collection (n=31), and had a neurologic or neurodevelopmental condition (n=28). On average, the initial clinical exome reports were issued 20 months before reanalysis. The researchers made a definitive diagnosis for 4 of the 40 participants—a causative, de novo variant in a relevant autosomal-dominant disease gene. […]