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Accurate identification and interpretation of genomic variants are essential for diagnosing rare diseases. The Solve-Rare Diseases Consortium (Solve-RD), a collaboration of clinical and molecular scientists from 37 expert centers across Europe, compiled a resource of clinical, pedigree, and genomic data (94.5% exomes, 5.5% genomes) from 6,447 individuals (3,592 male, 2,855 female) with previously undiagnosed rare diseases, across 6,004 families.
Through a collaborative, two-level expert review infrastructure, genetic diagnoses were made in 506 families (8.4%). Of the 552 disease-causing variants identified, 464 (84.1%) were single-nucleotide variants or short insertions/deletions, many located in novel disease genes, recently reclassified variants in ClinVar, or those reclassified by expert consensus within Solve-RD. Bioinformatics analyses helped identify the remaining 15.9% of variants (88). Additionally, ad hoc expert reviews diagnosed 249 families (4.1%), resulting in an overall diagnostic yield of 12.6%.
The infrastructure and collaborative networks established by Solve-RD provide a valuable blueprint for future large-scale international efforts. This resource is now open to the global rare-disease community for phenotype, variant, and gene queries, as well as genome-wide discoveries. Read the full article here. Read the full article here.