Fig. 4.

Predicted Isoforms and Relative Abundances as a Consequence of CHEK2 splice variant c.320-5 T > A. Intronic CHEK2 variant c.320-5 T > A weakens (6.8 to 4.1 bits) the natural acceptor of exon 3 (total of 15 exons). a ASSEDA reports the weakening of the natural exon strength (R _i,total reduced from 13.2 to 10.5 bits), which would result in reduced splicing of the exon otherwise known as leaky splicing. A pre-existing cryptic acceptor exists 92 nt upstream of the natural site, leading to a cryptic exon with similar strength to the mutated exon (R _i,total = 10.0 bits). This cryptic exon would contain 92 nt of the intron. b Before the mutation, isoform 1 is expected to be the only isoform expressed. c After the mutation, isoform 1 (wild-type) is predicted to become relatively less abundant and isoform 2 is expected to be expressed, although less abundant in relation to isoform 1