Antithrombin Dublin (-3 Val----Glu): an N-terminal variant which has an aberrant signal peptidase cleavage site

Antithrombin Dublin is an electrophoretically fast variant of antithrombin which has normal heparin affinity. Direct sequencing of amplified exon 2 revealed a Val----Glu substitution at position -3. N-terminal sequencing of antithrombin from two individuals, heterozygous for the Dublin mutation, showed the presence of a truncated antithrombin in which the N-terminal dipeptide is absent. We propose that the prepeptide mutation redirects signal peptidase cleavage to a site two amino acids downstream into the mature protein.