Purpose: 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.
Conclusion: 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.