NM_004006.3(DMD):c.2609T>G (p.Leu870Ter)

For DMD c.2609T>G (p.Leu870Ter), nonsense-suppression therapy is the most direct currently actionable variant-class strategy because the pathogenic event is a premature stop codon, making translational read-through more mechanistically aligned than approaches that require mutation-specific editing design.

ClinVar classifies DMD c.2609T>G (p.Leu870Ter) as pathogenic. The strongest direct clinical precedent for nonsense-mutation Duchenne muscular dystrophy is ataluren, which was developed specifically for premature stop codons and showed ambulatory benefit signals in randomized and pooled analyses of nmDMD cohorts (PMID:28781359; PMID:32851872). More recent placebo-controlled evidence from Study 041 also reported functional benefit in a prespecified nonsense-mutation subgroup consistent with the read-through mechanism (PMID:40843507). Because p.Leu870Ter is a bona fide stop-gain allele, it fits the biological class targeted by nonsense-suppression therapy even though the trials were not designed around this exact codon.

The evidence is for nonsense-mutation DMD as a class, not specifically for p.Leu870Ter. Clinical benefit from ataluren has remained debated across regulators and payers, and regulatory uncertainty increased after the European Medicines Agency recommended non-renewal of ataluren authorization in 2024. Any practical use also depends on disease stage, steroid background, geography, and access. This is therefore a mechanism-based therapeutic interpretation for a stop-gain DMD allele, not proof of variant-specific efficacy.