20.500.12556/DiRROS-28100 Comprehensive reanalysis for CNVs in ES data from unsolved rare disease cases results in new diagnoses We report the results of a comprehensive copy number variant (CNV) reanalysis of 9171 exome sequencing datasets from 5757 families affected by a rare disease (RD). The data reanalysed was extremely heterogeneous, having been generated using 28 different enrichment kits by 42 different research groups across Europe partnering in the Solve-RD project. Each research group had previously undertaken their own analysis of the data but failed to identify disease-causing variants.Weapplied three CNV calling algorithms tomaximise sensitivity, and rare CNVs overlapping genes of interest, provided by four partner European ReferenceNetworks, were taken forward for interpretation by clinical experts. This reanalysis has resulted in a molecular diagnosis being provided to 51 families in this sample, with ClinCNV performing the best of the three algorithms. We also identified partially explanatory pathogenic CNVs in a further 34 individuals. This work illustrates the value of reanalysing ES cold cases for CNVs. rare diseases reanalysis copy number variant disease-causing variants true false true Angleški jezik Ni določen Neznano 2026-03-10 09:49:56 2026-03-10 09:49:56 2026-03-11 03:59:14 0000-00-00 00:00:00 2024 0 0 Nasl. z nasl. zaslona; Opis vira z dne 20. 6. 2025; str. 1-24 [article no.] 49 Vol. 9 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 61:575 2056-7944 10.1038/s41525-024-00436-6 240092675 RAZ_Demidov_German_2024.pdf RAZ_Demidov_German_2024.pdf 1 BDAF1CA6674E665FEFD9737AEDA12CCF 85f40a3824d3d67f224bf8a3dc8cc6f9653d7e0ed8dabf19b1cabac78fa41b24 501f5108-1c5e-11f1-acf8-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=41523 https://doi.org/10.1038/s41525-024-00436-6 0 5a248ec3-1c5e-11f1-acf8-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=41524 Univerzitetni klinični center Ljubljana 0 0 0