Substitution grid that summarizes 2863-point missense variants in the F8 gene. The grid illustrates the total of missense variants that occurs for each defined amino acid change. All substitutions result from a single nucleotide change. Any grid substitutions that would require more than a single nucleotide change are shown in dark gray, although none were seen. Pale gray represents silent mutations; pale yellow represents substitutions that occur between 1 and 10 times; orange represents substitutions that occur between 11 and 20 times; and brown represents substitutions that occur ≥20 times. aa, amino acid.