Anne-Sophie Denommé-Pichon, Leslie Matalonga, Elke de Boer, Adam Jackson, Elisa Benetti, Siddharth Banka, Ange-Line Bruel, Andrea Ciolfi, Jill Clayton-Smith, Bruno Dallapiccola, Yannis Duffourd, Kornelia Ellwanger, Chiara Fallerini, Christian Gilissen, Holm Graessner, Tobias B Haack, Marketa Havlovicova, Alexander Hoischen, Nolwenn Jean-Marçais, Tjitske Kleefstra, Estrella López-Martín, Milan Macek, Maria Antonietta Mencarelli, Sébastien Moutton, Rolph Pfundt, Simone Pizzi, Manuel Posada, Francesca Clementina Radio, Alessandra Renieri, Caroline Rooryck, Lukas Ryba, Hana Safraou, Martin Schwarz, Marco Tartaglia, Christel Thauvin-Robinet, Julien Thevenon, Frédéric Tran Mau-Them, Aurélien Trimouille, Pavel Votypka, Bert B A de Vries, Marjolein H Willemsen, Birte Zurek, Alain Verloes, Christophe Philippe, Antonio Vitobello, Lisenka E L M Vissers, Laurence Faivre
PURPOSE: Within the Solve-RD project (https://solve-rd.eu/), the ERN-ITHACA (European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies) aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the "ClinVar low-hanging fruit" reanalysis, reasons for the failure of previous analyses and lessons learned. METHODS: Data from the first 3,576 exomes (1,522 probands and 2,054 relatives) collected from ERN-ITHACA was reanalyzed by the Solve-RD consortium by evaluating for the presence of SNV/indel already reported as (likely) pathogenic in ClinVar...
January 19, 2023: Genetics in Medicine: Official Journal of the American College of Medical Genetics