Figure 9.

Two possible models for the effect of the P3H1 variant on the splicing of P3H1 isoform a to form new isoforms. The variant CAG sequence is predicted to act as a constitutive splice acceptor site with 89% confidence, compared to an 8.6% chance for the consensus CAA sequence [13]. A GT sequence 116 bp later is predicted to act as a constitutive splice donor with 75% confidence. The use of this splice donor site gives the upper variant model an extra intron and exon and replaces the 51 amino acid residues encoded in exon 15 of isoform a with 44 alternative amino acids, with a frameshift in the final exon leading to an early stop codon. If the splice donor site is not used (lower variant model), intron 14 is reduced to 86 bp, and 49 codons are added from the former intron before a stop codon. In either case, the new C-terminal amino acid sequence is not functional.