Schematic of the locations of single nucleotide substitutions (single nucleotide variants [SNVs]), excluding nonsense variants; SVs in hemophilia A and B; and Exome Aggregation Consortium (ExAC) database SNVs relative to the F8 and F9 cDNAs. Scale schematics of the coding regions of the F8 gene (A, C) and the F9 gene (B, D). UTRs are depicted with blue filled boxes; exons are depicted as open boxes and numbered beneath. In panels A and B, above each gene, the frequency of unique SNV substitutions (missense, synonymous, splice, and UTR) by gene location is shown for males, and stacked histograms are colored by hemophilia disease severity (red, severe; purple, moderate–severe; light purple, mild–severe; blue, moderate; teal, mild–moderate; green, mild); histograms bins are 100 nucleotides. Below each gene, regions impacted by unique SVs are shown (red bars indicate deletions, blue bars indicate duplications, and pink hexagons indicate insertions). In panels C and D, above each gene, the incidence of unique SNV substitutions reported in the ExAC database of unrelated individuals is shown by gene location, and stacked histograms are colored by ExAC population frequency (red, 0.001% to 0.01%; purple, 0.01% to 0.1%; light purple, 0.1% to 1%; blue, 1% to 5%; teal, 5% to 20%; green, >20%); histogram bins are 100 nucleotides. For both genes, there was no annotated variation reported in the 3′UTRs after position c.*52.