FIGURE 1.

Trade‐off between sensitivity and PPV in reporting results. In individuals with monogenic cause of NDDs, the approach of reporting only Pathogenic and Likely Pathogenic variants will have high PPV but modest sensitivity, as some true positives are currently classified as VUSs. On the other hand, including VUS in the report will lead to high sensitivity but low PPV. Resolving VUS in the future, by improved computational and experimental tools and learning systems, is the key to improve sensitivity while maintaining high PPV.