The TADA-Denovo test considers two types of variants, de novo LGD and de novo severe missense (those predicted by PolyPhen2-HDIV to be “probably damaging” to protein function, abbreviated as “Mis3”; Adzhubei et al., 2010, 2013). The main input is the number of de novo LGD and number of de novo Mis3 variants per gene. Additionally, we utilized the included mutation rates (mu) for all human genes, which are based on Sanders et al. (2012). The test analyzes each of these event types separately and then combines the evidence in a Bayesian fashion, weighting each type of variant differently.
