2.3 | Candidate gene analysis for diagnostic exome cases
DES cases submitted as informative trios, defined as having samples from family members representative of both the maternal and paternal lineages, and that were negative after review of characterized gene-disease relationships are eligible for uncharacterized candidate gene analysis as previously described (Farwell-Hagman, 2017). If an identified characterized gene finding only accounts for part of a patient’s phenotype, uncharacterized genes can be analyzed for causes of the unaccounted-for clinical features. Uncharacterized genes that meet reporting criteria are considered candidate genes with uncertain clinical significance (Richards, 2015). Alterations in uncharacterized genes identified during analysis as having potential relevance undergo dual scientist and director review to determine if there is adequate evidence to report as a candidate finding (Smith, 2017).