SMN1 VUS plasmid data

<b>Clinical relevance of zebrafish for gene variants testing. </b><b>Proof-of-principle with</b><b> </b><b><i>SMN1/</i></b><b>SMA.</b>Spinal muscular atrophy (SMA) results from <i>SMN1</i> gene loss-of-function (LOF), with disease severity directly linked to the level of remaining SMN protein. Nusinersen, risdiplam and onasemnogene abeparvovec are revolutionary treatments but should ideally be implemented before clinical symptoms appear. Because of this, prenatal and newborn screenings are increasingly used to identify common <i>SMN1</i><i> </i>mutations and patients requiring therapy. However, for novel mutations, clinicians lack robust analytic tools to predict pathogenicity before irreversible damage occurs.To address this gap, we deployed a zebrafish model presenting <i>smn1</i>-LOF, exhibiting progressive motor defects and death by only six days of age. We evaluated two <i>SMN1-</i>variants (VUS) identified in newborn patients awaiting definite diagnosis and treatment recommendations.We demonstrated that while known pathogenic variants did not change the disease course, wild-type <i>SMN1</i> and both patient variants rescued SMA hallmarks in zebrafish, demonstrating the relevance of this approach for VUS-testing within a crucial timeframe for patients. Both VUS turned out to be non-pathogenic, and therapeutic costs of &gt;US$2 million per child were avoided.Beyond SMA, this study provides robust proof-of-principle that the zebrafish represents a powerful translational tool for VUS-analysis, and that such approaches should be considered in clinical settings for supporting diagnosis and treatment decisions.This dataset represents the plasmids created for <i>SMN1</i> VUS resolution.