REVIEW DNA variant databases improve test accuracy and phenotype prediction in Alport syndrome The International Alport Mutation Consortium & Judy Savige & Elisabet Ars & Richard G. H. Cotton & David Crockett & Hayat Dagher & Constantinos Deltas & Jie Ding & Frances Flinter & Genevieve Pont-Kingdon & Nizar Smaoui & Roser Torra & Helen Storey Received: 14 October 2012 / Revised: 2 January 2013 / Accepted: 3 January 2013 # IPNA 2013 Abstract X-linked Alport syndrome is a form of progres- sive renal failure caused by pathogenic variants in the COL4A5 gene. More than 700 variants have been described and a further 400 are estimated to be known to individual laboratories but are unpublished. The major genetic testing laboratories for X-linked Alport syndrome worldwide have established a Web-based database for published and unpublished COL4A5 variants (https://grenada.lumc.nl/ LOVD2/COL4A/home.php?select_db=COL4A5). This conforms with the recommendations of the Human Variome Project: it uses the Leiden Open Variation Database (LOVD) format, describes variants according to the human reference sequence with standardized nomenclature, indicates likely pathogenicity and associated clinical features, and credits the submitting laboratory. The database includes non- pathogenic and recurrent variants, and is linked to another COL4A5 mutation database and relevant bioinformatics sites. Access is free. Increasing the number of COL4A5 variants in the public domain helps patients, diagnostic laboratories, clinicians, and researchers. The database im- proves the accuracy and efficiency of genetic testing be- cause its variants are already categorized for pathogenicity. The description of further COL4A5 variants and clinical associations will improve our ability to predict phenotype and our understanding of collagen IV biochemistry. The database for X-linked Alport syndrome represents a model for databases in other inherited renal diseases. Keywords Alport syndrome . Gene variant . DNA database . Genetic testing . Inherited renal disease J. Savige : H. Dagher Department of Medicine (Northern Health), The University of Melbourne, Epping, VIC, Australia E. Ars Nephrology Department, Fundacio Puigvert, Barcelona, Spain R. G. H. Cotton Human Variome Project, The University of Melbourne, Parkville, VIC, Australia D. Crockett : G. Pont-Kingdon ARUP Laboratories, ARUP Institute of Clinical and Experimental Pathology, Salt Lake City, UT, USA C. Deltas Molecular Medicine Research Center and Laboratory of Molecular and Medical Genetics, Department of Biological Sciences, University of Cyprus, Nicosia, Cyprus J. Ding Pediatric Department, Peking University First Hospital, Beijing, China F. Flinter Department of Clinical Genetics, Guy’ s and St Thomas’ NHS Trust Foundation, London, UK N. Smaoui GeneDx, Gaithersburg, MD, USA R. Torra Molecular Biology Laboratory, Fundacio Puigvert, Universitat Autonoma de Barcelona, Barcelona, Spain H. Storey GSTS Pathology, Guy’ s and St Thomas’ NHS Trust Foundation, London, UK J. Savige (*) The University of Melbourne (AH/NH), The Northern Hospital, Cooper, Epping, VIC 3076, Australia e-mail: jasavige@unimelb.edu.au Pediatr Nephrol DOI 10.1007/s00467-013-2486-8