A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Anne-Sophie Denommé-Pichon, 1; Leslie Matalonga, 2; Elke De Boer, 3; Adam Jackson, 4; Elisa Benetti, 5; Siddharth Banka, 4; Ange-Line Bruel, 6; Andrea Ciolfi, 7; Jill Clayton-Smith, 4; Bruno Dallapiccola, 7; Yannis Duffourd, 6; Kornelia Ellwanger, 8; Chiara Fallerini, 9; Christian Gilissen 10,; Holm Graessner, 8; B Haack 8, Tobias; Marketa Havlovicova 11,; Alexander Hoischen 12,; Nolwenn Jean-Marçais 13,; Tjitske Kleefstra 14,; Estrella López-Martín 15,; Milan Macek 11,; Maria Antonietta Mencarelli 16,; Sébastien Moutton 17,; Rolph Pfundt, 3; Simone Pizzi, 7; Manuel Posada 15,; Francesca Clementina Radio, 7; Alessandra Renieri 18,; Caroline Rooryck 19,; Lukas Ryba 11,; Hana Safraou, 6; Martin Schwarz 11,; Marco Tartaglia, 7; Christel Thauvin-Robinet 20,; Julien Thevenon 17,; Frédéric Tran Mau-Them, 6; Aurélien Trimouille 21,; Pavel Votypka 11,; B A De Vries 3, Bert; H Willemsen 3, Marjolein; Birte Zurek, 8; Alain Verloes 22,; Christophe Philippe, 6; DITF-ITHACA, Solve-RD; Solve-RD SNV-indel Working Group,; Consortia, Solve-RD; Group, Orphanomix; Antonio Vitobello, 6; E L M Vissers 3, Lisenka; Laurence Faivre 23,; Balestrini, Simona; Guerrini, Renzo

doi:10.1016/j.gim.2023.100018

Within the Solve-RD project (https://solve-rd.eu/), the 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.

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing / Anne-Sophie Denommé-Pichon 1, L.M.2., Solve-RD DITF-ITHACA, Solve-RD SNV-indel Working Group, Solve-RD Consortia, Orphanomix Group, Antonio Vitobello 6, L.E.L.M.V.3.. - In: GENETICS IN MEDICINE. - ISSN 1530-0366. - ELETTRONICO. - (2023), pp. 0-0. [10.1016/j.gim.2023.100018]