NCBIs ClinVar: data archive and tools for human variation of medical interest. D. Maglott, S. Chitipiralla, D. Church, M. Feolo, J. Garner, W. Jang, J. Lee, R. Maiti, J. Ostell, L. Phan, G. Riley, W. S. Rubinstein, D. Shao, S. Sherry, K. Sirotkin, R. Tully, R. Villamarin, M. Ward Natl Ctr Biotech Info, NIH/NLM, Bethesda, MD.

   The discovery of human sequence variation is outpacing development of resources and tools to maintain information about clinical significance. Clinical and experimental evidence on which interpretations are based have frequently been captured in local databases, as unstructured data or without standardized usage. Thus the primary use cases for maintaining these data--namely (1) identification of variation known to be disease-related, (2) identification of variation not thought to be disease-related and (3) automatable re-evaluationare difficult. The National Center for Biotechnology Information (NCBI) established ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/) to solve these problems by centralizing management of these data. ClinVar is a versioned archive of submissions reporting genotype, phenotype, clinical interpretation and supporting evidence, including observations in affected or unaffected individuals, animal models, in vitro assays, and in silico predictions. Once data are accumulated in standardized structures, they can be reviewed by experts. ClinVar provides infrastructure for such deliberations, and captures decisions attributed to the group contributing the intellectual effort. In other words, ClinVar accepts both submitted reviews of clinical interpretation by authoritative groups and primary data. To identify genes and variations about which some assessment of pathogenicity has been made, ClinVar integrates data from OMIM, GeneReviews, the Genetic Testing Registry, locus-specific databases, as well as multiple testing laboratories. Common variation without such assessments are also reported. Users can interrogate ClinVar starting at different points--by genomic location, by phenotype, by gene, by associated citationto name a few. The user can retrieve data interactively, or download reports after submitting large sets of variation calls, such as from high-throughput sequencing. Data are also accessible by interactive browsing, ftp, and NCBI E-utilities. These modes are intended to facilitate integration of ClinVar into clinical interpretation analysis workflows. ClinVar welcomes data sharing with resources maintaining information on human variation. For example, ClinVar is the data repository for the proposed U.S. node of the Human Variome Project (HVP).
    This presentation will review data submission, data access, and current status of ClinVar.

You may contact the first author (during and after the meeting) at