F5 and hyperinsulinemic hypoglycemia, familial, 4: Actually, at least two additional missense substitutions causing FV deficiency were revealed to be splicing defects: (i) the p.Gln509His mutation, which is an apparent missense activating a cryptic donor splice site [14]; and (ii) the p.Ala1779Thr substitution, which interferes with intron 16 splicing [12].