Next steps
Trio testing is powerful for the identification of de novo and biallelic alterations confirmed in trans . In fact, 90.53% of our GeneMatcher entries were for autosomal dominant de novooccurrences or autosomal recessive reports. Future identification of elusive disease genes, such as those with lower penetrance or complex inheritance patterns, will require extensive involvement in data-sharing initiatives to further power disease gene discovery efforts. This will be even more important as clinical DES use extends into varied clinical settings. For example, expanding the clinical uses into the prenatal clinic may ascertain more severe phenotypes not compatible with life and therefore yet to be identified. As more commercially available panels are run on an exome backbone, the ability to tailor gene content based on the latest literature and proactively provide reclassification results can extend to other testing platforms. Ongoing participation in GeneMatcher and other Matchmaker Exchange platforms will heighten the diagnostic and disease gene discovery power of DES.