Figure 1. Systematic reanalysis increases diagnostic rates in two patient series referred to clinical exome sequencing.
The left (Cohort #1, N=250) and the right (Cohort #2, N=2000) panels depict the molecular diagnostic rate changes from the original rates, evidenced by respective publications3,4, and the reanalysis rates. The yield alteration originates from patients whose diagnostic molecular findings changed from zero to one or more (new diagnosis, highlighted in red in the reanalysis bar), from one to two or more (multilocus pathogenic variation; the white segment below the red segment in the reanalysis bar), and from one to zero (overturned molecular diagnosis, see Supplemental Appendix). The white segment above the red segment represents the proportion of patients who received a partial diagnosis from reanalysis (n=2 for Cohort #1, n=5 for Cohort #2), which is not counted towards the diagnostic rate. The Pareto charts to the right of the bar charts illustrate the breakdown of the interpretive reasons contributing to each new molecular diagnosis, with cumulative counts from each category shown in the bottom axis and the cumulative percentages shown in the top axis.