WGS and WES have been used successfully to detect somatic SNVs in family-based studies of Mendelian disease and large-scale sequencing studies of human patient cohorts (2). To identify SNVs, most computational approaches compare call sets generated from an affected sample to those generated from a matched healthy/unaffected sample and/or a control population. These comparisons allow the identification and subsequent exclusion of germline polymorphisms from downstream analyses; however, care must be taken to ensure that any candidate somatic mutations are not germline variants that were missed in the matched control. In general, variant callers initially developed to detect mutations in cancer offer higher sensitivity for detecting mosaic SNVs when compared with standard approaches used to detect germline variants (85, 86).
