Pediatric Nephrology

, Volume 29, Issue 6, pp 971–977 | Cite as

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


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than 700 variants have been described and a further 400 are estimated to be known to individual laboratories but are unpublished.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testing laboratories for X-linked Alport syndrome worldwide have established a Web-based database for published and unpublished COL4A5 variants ( This conforms with the recommendations of the Human Variome Project: it uses the Leiden Open Variation Database (LOVD) format, describes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.


Alport syndrome Gene variant DNA database Genetic testing Inherited renal disease 


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Copyright information

© IPNA 2013

Authors and Affiliations

  • The International Alport Mutation Consortium
  • Judy Savige
    • 1
    • 11
  • Elisabet Ars
    • 2
  • Richard G. H. Cotton
    • 3
  • David Crockett
    • 4
  • Hayat Dagher
    • 1
  • Constantinos Deltas
    • 5
  • Jie Ding
    • 6
  • Frances Flinter
    • 7
  • Genevieve Pont-Kingdon
    • 4
  • Nizar Smaoui
    • 8
  • Roser Torra
    • 9
  • Helen Storey
    • 10
  1. 1.Department of Medicine (Northern Health)The University of MelbourneEppingAustralia
  2. 2.Nephrology Department, Fundacio PuigvertBarcelonaSpain
  3. 3.Human Variome ProjectThe University of MelbourneParkvilleAustralia
  4. 4.ARUP LaboratoriesARUP Institute of Clinical and Experimental PathologySalt Lake CityUSA
  5. 5.Molecular Medicine Research Center and Laboratory of Molecular and Medical Genetics, Department of Biological SciencesUniversity of CyprusNicosiaCyprus
  6. 6.Pediatric DepartmentPeking University First HospitalBeijingChina
  7. 7.Department of Clinical GeneticsGuy’s and St Thomas’ NHS Trust FoundationLondonUK
  8. 8.GeneDxGaithersburgUSA
  9. 9.Molecular Biology Laboratory, Fundacio PuigvertUniversitat Autonoma de BarcelonaBarcelonaSpain
  10. 10.GSTS PathologyGuy’s and St Thomas’ NHS Trust FoundationLondonUK
  11. 11.The University of Melbourne (AH/NH), The Northern HospitalEppingAustralia

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