Schematic of predicted effect on VWF splicing by the synonymous VWF c.7464C>T variant. (Left) Normally splicing begins with transcription of a VWF pre-mRNA (partial cartoon of VWF exons 44-45 shown on top), followed by docking of U1snRNA (yellow) for the 5′ (donor) splice site during pre-spliceosome formation (middle) and multiple intermediate steps (spliceosome assembly, catalysis, intron lariat formation; not shown); completion of splicing results in spliced mRNA (bottom). (Right) In silico model predicted effect of the synonymous VWF substitution c.7464C>T in exon 44 (dark star) shown transcribed in the pre-mRNA (top); the c.7464C>T variant is predicted to cause a hairpin in the secondary RNA structure (hash-marked exon) disrupting the VWF exon 44 5′ss U1snRNA docking site (red Xs); the failure of U1snRNA to dock would result in retention of VWF intron 44 sequence and an abnormal and prematurely truncated VWF protein.