Table 1.

RapSeq selection criteria

1) Meets our definition of “high acuity”	Patients present with respiratory and/or cardiovascular failure, encephalopathy, profound hypotonia, complex brain malformations, severe metabolic disturbance, or multiple congenital anomalies (without a known syndrome), unusually severe or prolonged disease, or multi‐system organ failure.
2) Making a diagnosis will alter acute decision‐making	Consensus that time‐critical treatment and/or change in care plan might be anticipated based on the results. Examples include administration of medications and diagnostic testing that could confirm a diagnosis. Importantly, irreversible decisions such as withdrawal of care are not based solely on genetic testing, especially in case of preliminary results.
3) The patient's disease is plausibly monogenic	The presentation is within a spectrum with likely genetic causes, but for which a clear diagnosis cannot be made. Examples of conditions where this would not be the case include isolated congenital diaphragmatic hernia or isolated congenital heart disease.
4) Alternate testing is unavailable, more costly, or protracted	Examples where alternative testing is more appropriate include chromosomes for suspected trisomy and single gene testing or multigene panels for clear‐cut genetic conditions (unless turn‐around‐time is excessive). Tests that might best be done in parallel include chromosome microarray, SMA testing, MRI, and metabolic testing. Tests that might best be done in series include muscle biopsy, CSF neurotransmitters.
5) A trio (both parents and patient) is available.	For a rapid interpretation, only trios are tested because this speeds the filtering process, allows identification of de novo variants, and establishes phase of potentially recessive alleles without the delays due to Sanger validation.