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).