RT Journal Article
SR Electronic
T1 Evaluating the clinical validity of gene-disease associations: an evidence-based framework developed by the Clinical Genome Resource
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 111039
DO 10.1101/111039
A1 Natasha T. Strande
A1 Erin Rooney Riggs
A1 Adam H. Buchanan
A1 Ozge Ceyhan-Birsoy
A1 Marina DiStefano
A1 Selina S. Dwight
A1 Jenny Goldstein
A1 Rajarshi Ghosh
A1 Bryce A. Seifert
A1 Tam P. Sneddon
A1 Matt W. Wright
A1 Laura V. Milko
A1 J. Michael Cherry
A1 Monica A. Giovanni
A1 Michael F. Murray
A1 Julianne M. O’Daniel
A1 Erin M. Ramos
A1 Avni B. Santani
A1 Alan F. Scott
A1 Sharon E. Plon
A1 Heidi L. Rehm
A1 Christa L. Martin
A1 Jonathan S. Berg
YR 2017
UL http://biorxiv.org/content/early/2017/03/01/111039.abstract
AB 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.