Model Validation

Comparing Becker's exon-skipping predictions against published clinical data and FDA-approved therapies. Each case is run through our analysis engine and checked against known outcomes from peer-reviewed literature.

Checks Passed

Checks Failed

Test Cases

100%

Accuracy

DMD Exon 48-50 Deletion → Exon 51 Skip

DMD · deletion of exons 48, 49, 50

4/4 checks passed

Our Model

Known Literature

Skip Target

Exon 51

Frame Restored

Yes

Protein Retained

94%

90-96%

Matched Therapy

Eteplirsen (Exondys 51); SRP-5051

Eteplirsen (Exondys 51) — FDA approved 2016

Model Details

Frameshift

+1bp

Confidence

high

Predicted Protein

3,475 / 3,685 aa

Strategies Found

Lost Domains

SR19, hinge-3

Literature Reference

Deletion of exons 48-50 is one of the most common DMD mutations (~4% of patients). Skipping exon 51 restores the reading frame, producing a truncated but partially functional dystrophin. Eteplirsen was the first exon-skipping drug approved for DMD. Clinical trials showed stabilization of 6-minute walk distance.

Cirak et al., Lancet 2011; FDA label for Eteplirsen →

DMD Exon 52 Deletion → Exon 53 Skip

DMD · deletion of exon 52

4/4 checks passed

Our Model

Known Literature

Skip Target

Exon 53

Frame Restored

Yes

Protein Retained

97%

90-98%

Matched Therapy

Viltolarsen (Viltepso); Golodirsen (Vyondys 53); WVE-N531

Viltolarsen (Viltepso) — FDA approved 2020; Golodirsen (Vyondys 53) — FDA approved 2019

Model Details

Frameshift

+1bp

Confidence

high

Predicted Protein

3,575 / 3,685 aa

Strategies Found

Lost Domains

SR20

Literature Reference

Exon 52 deletion causes frameshift. Skipping exon 53 restores the reading frame with minimal protein loss (central rod domain). Two FDA-approved drugs target exon 53 skipping, applicable to ~8% of DMD patients.

Frank et al., Neurology 2020; FDA labels for Viltolarsen & Golodirsen →

DMD Exon 44 Deletion → Exon 45 Skip

DMD · deletion of exon 44

4/4 checks passed

Our Model

Known Literature

Skip Target

Exon 45

Frame Restored

Yes

Protein Retained

97%

93-99%

Matched Therapy

Casimersen (Amondys 45); Renadirsen (DS-5141b)

Casimersen (Amondys 45) — FDA approved 2021

Model Details

Frameshift

+1bp

Confidence

high

Predicted Protein

3,577 / 3,685 aa

Strategies Found

Literature Reference

Exon 44 deletion causes a +1bp frameshift. Skipping exon 45 restores the reading frame with only 324bp removed from the central rod domain (spectrin repeats 17-18). Casimersen is an FDA-approved PMO targeting exon 45, applicable to ~8% of DMD patients. Clinical data shows increased dystrophin expression in skeletal muscle.

Sarepta Therapeutics FDA label; Wagner et al., NEJM 2021 →

Validation Methodology

Skip Target: Does our model identify the same exon(s) to skip as established in clinical practice and published literature?
Frame Restored: Does the skip strategy correctly restore the reading frame (total removed bp divisible by 3)?
Protein Retained: Is the predicted protein length within the expected range from published Becker phenotype data?
Matched Therapy: Does our therapy database correctly identify FDA-approved or clinical-trial drugs for the predicted skip?

Exon data is sourced from Ensembl (ENST00000357033 for DMD, ENST00000307340 for USH2A) and cross-referenced with NCBI RefSeq. Coding bp are computed by clipping mRNA exon coordinates to CDS boundaries, excluding UTR.