James L. Shepherdson,^1,46 Katie Hutchison,^2,46 Dilan Wellalage Don,^3,46 George McGillivray,^4,5 Tae-Ik Choi,³ Carolyn A. Allan,⁶ David J. Amor,^5,7 Siddharth Banka,^8,9 Donald G. Basel,¹⁰ Laura D. Buch,¹¹ Deanna Alexis Carere,¹² Rene´e Carroll,¹³ Jill Clayton-Smith,¹⁴ Ali Crawford,¹⁵ Morten Dunø,¹⁶ Laurence Faivre,^17,18 Christopher P. Gilfillan,^19,20 Nina B. Gold,^21,22 Karen W. Gripp,²³ Emma Hobson,²⁴ Alexander M. Holtz,²⁵ A. Micheil Innes,²⁶ Bertrand Isidor,^27,28 Adam Jackson,^8,9 Panagiotis Katsonis,²⁹ Leila Amel Riazat Kesh,²⁴ Genomics England Research Consortium, Se´bastien Ku¨ry,^27,28 Franc¸ois Lecoquierre,³⁰ Paul Lockhart,^5,7 Julien Maraval,17^,18 Naomichi Matsumoto,³¹ Julie McCarrier,¹⁰ Josephine McCarthy,²⁰ Noriko Miyake,^31,32 Lip Hen Moey,³³ Andrea H. Ne´meth,^34,35 Elsebet Østergaard,^16,36 Rushina Patel,³⁷ Kate Pope,⁵ Jennifer E. Posey,²⁹ Rhonda E. Schnur,¹² Marie Shaw,¹³ Elliot Stolerman,¹¹ Julie P. Taylor,¹⁵ Erin Wadman,²³ Emma Wakeling,³⁸ Susan M. White,^4,5,7 Lawrence C. Wong,³⁹ James R. Lupski,^29,40,41,42 Olivier Lichtarge,²⁹ Mark A. Corbett,¹³ Jozef Gecz,^13,43 Charles M. Nicolet,² Peggy J. Farnham,^2,45 Cheol-Hee Kim,^3,45,* and Marwan Shinawi^44,45,*

¹Medical Scientist Training Program, Washington University School of Medicine, St. Louis, MO, USA; 

²Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; 

³Department of Biology, Chungnam National University, Daejeon 34134, Korea; 

⁴Victorian Clinical Genetics Services, Parkville, VIC 3052, Australia; 

⁵Murdoch Children’s Research Institute, Parkville, VIC 3052, Australia; 

⁶Hudson Institute of Medical Research, Monash University, and Department of Endocrinology, Monash Health, Melbourne, Australia; 

⁷Department of Paediatrics, The University of Melbourne, Parkville 3052, VIC, Australia; 

⁸Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; 

⁹Manchester Centre for Genomic Medicine, St Mary’s Hospital, Manchester University NHS Foundation Trust, Health Innovation Manchester, Manchester, UK; 

¹⁰Division of Genetics, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA; 

¹¹Greenwood Genetic Center, Greenwood, SC, USA; 

¹²GeneDx, Gaithersburg, MD 20877, USA; 

¹³Adelaide Medical School and Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia; 

¹⁴Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester, UK; 

¹⁵Medical Genomics Research, Illumina Inc, San Diego, CA, USA; 

¹⁶Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; 

¹⁷Centre de Re´fe´rence Anomalies du De´veloppement et Syndromes Malformatifs, FHU TRANSLAD, Hoˆpital d’Enfants, Dijon, France; 

¹⁸INSERM UMR1231, Equipe GAD, Universite´ de Bourgogne-Franche Comte´, 21000 Dijon, France; 

¹⁹Eastern Health Clinical School, Monash University, Melbourne, VIC, Australia; 

²⁰Department of Endocrinology, Eastern Health, Box Hill Hospital, Melbourne, VIC, Australia; 

²¹Harvard Medical School, Boston, MA, USA; 

²²Division of Medical Genetics and Metabolism, Massachusetts General Hospital, Boston, MA, USA; 

²³Division of Medical Genetics, Nemours Children’s Hospital, Wilmington, DE, USA; 

²⁴Yorkshire Regional Genetics Service, Leeds Teaching Hospitals NHS Trust, Department of Clinical Genetics, Chapel Allerton Hospital, Leeds, UK; 

²⁵Division of Genetics and Genomics, Boston Children’s Hospital, Boston, MA, USA; 

²⁶Departments of Medical Genetics and Pediatrics and Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; 

²⁷Nantes Universite´, CHU Nantes, Service de Ge´ne´tique Me´dicale, 44000 Nantes, France; 

²⁸Nantes Universite´, CHU Nantes, CNRS, INSERM, l’institut du Thorax, 44000 Nantes, France; 

²⁹Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; 

³⁰Univ Rouen Normandie, Inserm U1245 and CHU Rouen, Department of Genetics and Reference Center for Developmental Disorders, 76000 Rouen, France; 

³¹Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan; 

³²Department of Human Genetics, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan; 

³³Department of Genetics, Penang General Hospital, George Town, Penang, Malaysia; 

³⁴Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; 

³⁵Oxford Centre for Genomic Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; 

³⁶Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 

³⁷Medical Genetics, Kaiser Permanente Oakland Medical Center, Oakland, CA, USA; 

³⁸North East Thames Regional Genetic Service, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK; 

³⁹Medical Genetics, Kaiser Permanente Downey Medical Center, Downey, CA, USA; 

⁴⁰Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA; 

⁴¹Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA; 

⁴²Texas Children’s Hospital, Houston, TX, USA; 

⁴³South Australian Health and Medical Research Institute, Adelaide, SA, Australia; 

⁴⁴Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA

⁴⁵Senior authors 

⁴⁶These authors contributed equally

*Correspondence: C.-H.K., M.S.