To Confirm or Not to Confirm

Traditional clinical genetic testing involved evaluating single variants or genes or, at most, a handful of genes using Sanger methods. Significant or potentially significant variants were confirmed. This was not an issue because there were so few to worry about. With the advent of highly parallel, genome-scale sequencing, the number of variants to confirm rose from a few to potentially hundreds or thousands.  Laboratories and clinicians alike struggled with the urgent questions that arose: How many should be confirmed? What technology should be used to do it?  This issue has become more prominent as some testing companies have dropped confirmation altogether while, at the other end of spectrum, others recoil at the thought of providing information that may include errors. The current dilemma is: Should we still confirm variants or is that simply a quaint notion that can be discarded as we move into the NGS era? We will discuss the various sequencing platforms and the potential risks and rewards of (skipping) confirmation.