Pediatric Nephrology

, Volume 30, Issue 11, pp 1893–1901 | Cite as

The Human Variome Project: ensuring the quality of DNA variant databases in inherited renal disease

  • Judy Savige
  • Raymond Dalgleish
  • Richard GH Cotton
  • Johan T den Dunnen
  • Finlay Macrae
  • Sue Povey


A recent review identified 60 common inherited renal diseases caused by DNA variants in 132 different genes. These diseases can be diagnosed with DNA sequencing, but each gene probably also has a thousand normal variants. Many more normal variants have been characterised by individual laboratories than are reported in the literature or found in publicly accessible collections. At present, testing laboratories must assess each novel change they identify for pathogenicity, even when this has been done elsewhere previously, and the distinction between normal and disease-associated variants is particularly an issue with the recent surge in exomic sequencing and gene discovery projects. The Human Variome Project recommends the establishment of gene-specific DNA variant databases to facilitate the sharing of DNA variants and decisions about likely disease causation. Databases improve diagnostic accuracy and testing efficiency, and reduce costs. They also help with genotype–phenotype correlations and predictive algorithms. The Human Variome Project advocates databases that use standardised descriptions, are up-to-date, include clinical information and are freely available. Currently, the genes affected in the most common inherited renal diseases correspond to 350 different variant databases, many of which are incomplete or have insufficient clinical details for genotype–phenotype correlations. Assistance is needed from nephrologists to maximise the usefulness of these databases for the diagnosis and management of inherited renal disease.


DNA variant database Genetic variant Inherited disease Phenotype Pathogenicity 



The authors of this manuscript are all members of the Human Variome Project, but have no financial disclosures or conflicts of interest to declare. The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement number 200754—the GEN2PHEN project. This funding source played no role in the production of this manuscript. This work was completed while JS was a Visiting Academic within the Research Department of Genetics, Evolution and the Environment at University College London.


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Copyright information

© IPNA 2014

Authors and Affiliations

  • Judy Savige
    • 1
    • 7
  • Raymond Dalgleish
    • 2
  • Richard GH Cotton
    • 3
  • Johan T den Dunnen
    • 4
  • Finlay Macrae
    • 1
    • 5
  • Sue Povey
    • 6
  1. 1.The University of MelbourneMelbourne HealthMelbourneAustralia
  2. 2.Department of GeneticsUniversity of LeicesterLeicesterUK
  3. 3.Human Variome ProjectThe University of MelbourneMelbourneAustralia
  4. 4.Human and Clinical GeneticsLeiden University Medical CenterLeidenThe Netherlands
  5. 5.Colorectal Medicine and GeneticsThe Royal Melbourne HospitalParkvilleAustralia
  6. 6.Research Department of Genetics, Evolution and EnvironmentUniversity College LondonLondonUK
  7. 7.Department of Medicine, Royal Melbourne HospitalThe University of MelbourneParkvilleAustralia

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