title: Three-year experience of a CAP/ACMG methods-based external proficiency testing program for laboratories offering DNA sequencing for rare inherited disorders.
abstract: OBJECTIVE
  Thousands of genetic tests are now offered clinically, but many are for rare disorders that are offered by only a few laboratories. The classic approach to disease-specific external proficiency testing programs is not feasible for such testing, yet calls have been made to provide external oversight.
  
  
  METHODS
  A methods-based Sequencing Educational Challenge Survey was launched in 2010, under joint administration of the College of American Pathologists and the American College of Medical Genetics and Genomics. Three sets of Sanger ABI sequence data were distributed twice per year. Participants were asked to identify, formally name, and interpret the sequence variant(s).
  
  
  RESULTS
  Between 2010 and 2012, 117 laboratories participated. Using a proposed assessment scheme (e.g., at least 10 of 12 components correct), 98.3% of the 67 US participants had acceptable performance (235 of 239 challenges; 95% confidence interval: 95.8-99.5%) as compared with 88.9% (136 of 153; 95% confidence interval: 82.8-93.4%) for the 50 international participants.
  
  
  CONCLUSIONS
  These data provide a high level of confidence that most US laboratories offering rare disease testing are providing consistent and reliable clinical interpretations. Methods-based proficiency testing programs may be one part of the solution to assessing genetic testing based on next-generation sequencing technology.
authors.affiliation: Department of Molecular and Medical Genetics, Knight Diagnostic Laboratories, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: C Sue
authors.initials: CS
authors.lastname: Richards
authors.affiliation: Department of Pathology, Women & Infants Hospital, Alpert School of Medicine at Brown University, Providence, Rhode Island, USA.
authors.forename: Glenn E
authors.initials: GE
authors.lastname: Palomaki
authors.affiliation: Department of Molecular Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Felicitas L
authors.initials: FL
authors.lastname: Lacbawan
authors.affiliation: Department of Pathology, University of Utah, and ARUP Laboratories, Salt Lake City, Utah, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Lyon
authors.affiliation: Detroit Medical Center and Departments of Pathology and Pediatrics and Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan, USA.
authors.forename: Gerald L
authors.initials: GL
authors.lastname: Feldman
mesh_terms: D003625:Data Collection; D005820:Genetic Testing / Q000592:standards* / Q000706:statistics & numerical data; D006801:Humans; D007753:Laboratories / Q000592:standards*; D059021:Laboratory Proficiency Testing / Q000706:statistics & numerical data*; D035583:Rare Diseases / Q000175:diagnosis* / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000592:standards*; D012955:Societies, Medical; D014481:United States