GFM1 and hemophilia B: As an grouped analysis, 215 mutations in the first five exons showed significant association to the clinical severity of hemophilia B based on analysis by SIFT, PolyPhen-2 HumDiv, MutationAssessor, SNAP2 (P ≤ 0.05), and wgP4 (P = 0.017), but this association was not significant for mutations in EGF-1, as well as in the signal peptide and propeptide.