TY - JOUR T1 - Evaluating the clinical validity of gene-disease associations: an evidence-based framework developed by the Clinical Genome Resource JF - bioRxiv DO - 10.1101/111039 SP - 111039 AU - Natasha T. Strande AU - Erin Rooney Riggs AU - Adam H. Buchanan AU - Ozge Ceyhan-Birsoy AU - Marina DiStefano AU - Selina S. Dwight AU - Jenny Goldstein AU - Rajarshi Ghosh AU - Bryce A. Seifert AU - Tam P. Sneddon AU - Matt W. Wright AU - Laura V. Milko AU - J. Michael Cherry AU - Monica A. Giovanni AU - Michael F. Murray AU - Julianne M. O’Daniel AU - Erin M. Ramos AU - Avni B. Santani AU - Alan F. Scott AU - Sharon E. Plon AU - Heidi L. Rehm AU - Christa L. Martin AU - Jonathan S. Berg Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/02/22/111039.abstract N2 - With advances in genomic sequencing technology, the number of reported gene-disease relationships has rapidly expanded. However, the evidence supporting these claims varies widely, confounding accurate evaluation of genomic variation in a clinical setting. Despite the critical need to differentiate clinically valid relationships from less well-substantiated relationships, currently no standard guidelines for such evaluation exist. Thus the NIH-funded Clinical Genome Resource (ClinGen) has developed a framework to define and evaluate the clinical validity of gene-disease pairs across a variety of Mendelian disorders. Relevant genetic and experimental evidence supporting or contradicting a gene-disease relationship is evaluated semi-quantitatively and assigned a preliminary classification: “Definitive”, “Strong”, “Moderate”, “Limited”, “No Reported Evidence” or “Conflicting Evidence.” Classifications are reviewed and confirmed or adjusted based on clinical expertise of appropriate disease experts. This evidence-based, systematic method to assess the strength of gene-disease relationships will facilitate more knowledgeable utilization of genomic variants in clinical and research settings. ER -