title: DNA variant databases improve test accuracy and phenotype prediction in Alport syndrome.
abstract: X-linked Alport syndrome is a form of progressive 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than 700 variants have been described and a further 400 are estimated to be known to individual laboratories but are unpublished.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testing laboratories for X-linked Alport syndrome worldwide have established a Web-based database for published and unpublished COL4A5 variants ( https://grenada.lumc.nl/LOVD2/COL4A/home.php?select_db=COL4A5 ).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 improves the accuracy and efficiency of genetic testing because 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.
authors.forename: Judy
authors.initials: J
authors.lastname: Savige
authors.forename: Elisabet
authors.initials: E
authors.lastname: Ars
authors.forename: Richard G H
authors.initials: RG
authors.lastname: Cotton
authors.forename: David
authors.initials: D
authors.lastname: Crockett
authors.forename: Hayat
authors.initials: H
authors.lastname: Dagher
authors.forename: Constantinos
authors.initials: C
authors.lastname: Deltas
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.forename: Frances
authors.initials: F
authors.lastname: Flinter
authors.forename: Genevieve
authors.initials: G
authors.lastname: Pont-Kingdon
authors.forename: Nizar
authors.initials: N
authors.lastname: Smaoui
authors.forename: Roser
authors.initials: R
authors.lastname: Torra
authors.forename: Helen
authors.initials: H
authors.lastname: Storey
mesh_terms: D024141:Collagen Type IV / Q000235:genetics*; D030561:Databases, Nucleic Acid; D006801:Humans; D009394:Nephritis, Hereditary / Q000235:genetics*; D010641:Phenotype
chemical_list: C478159:COL4A5 protein, human; D024141:Collagen Type IV