The Working Group tried to include conditions on the list where confirmatory approaches for medical diagnosis would be available, although we recognized that this standard could not be met for all of the conditions listed. The Working Group prioritized disorders where preventative measures and/or treatments were available and disorders in which individuals with pathogenic mutations might be asymptomatic for long periods of time. In most cases, the Working Group recommended restricting the variants to be reported as incidental findings to those that meet criteria for reporting as Pathogenic (noted as “Sequence variation is previously reported and is a recognized cause of the disorder” or “Sequence variation is previously unreported and is of the type which is expected to cause the disorder”.20 These were chosen because we recognized the challenge of attempting to report and interpret variants of unknown significance as incidental findings. Given the low prior probability that an individual has a monogenic disorder that could be identified incidentally through exome or genome sequencing, we recommended that only variants with a higher likelihood of causing disease should be reported as incidental findings although we recognize that there are limited data available in many cases to make this assessment.
