It is becoming increasingly challenging to keep up with the ever-expanding gene space of inborn errors of immunity (IEIs) and the genetic paradigms these are introducing or reinforcing. With the monogenic IEIs, even very robust and highly suggestive clinical phenotypes may be associated with negative or equivocal clinical genetic testing. In these situations, we often find ourselves asking the question: "It is hiding in plain sight? Is it not there or did we just not find it?". Thus, a negative genetic testing report is often just the beginning of an iterative diagnostic process.

Some of the reasons we may fail to detect a disease-causing change are inherent to the limitations of current technology, while others may be knowledge-based. In terms of the latter, we have limited control over the pace at which new variants, genes and disorders are discovered. It is always gratifying when an IEI patient is able access and be brought to medical attention, receive molecular diagnosis, and then have their story shared with the greater biomedical community. However, there are likely many more individuals out there we may never meet or learn from.