Study design and methods. The study included four cohorts: MD Anderson (MDA), National Cancer Institute (NCI), Dana-Farber Cancer Institute (DFCI), and Children's Hospital of Philadelphia (CHOP) in our study. A subset of families within each cohort have mutation testing results from the parents, and therefore the true DNM status is known. These families form the validation set of our study. In the other families, the family members’ DNM statuses are unknown, and they form the discovery set.