Table 1.

	Preconception Carrier Screening	Prenatal Including PGD & NIPT	Newborn Screening	Suspected Rare Disease	Oncology and Tumor Profiling	Common Disease	Pharmacogenomics
Test Purpose	Risk assessment	Risk assessment and diagnosis	Therapeutic intervention, risk assessment, disease monitoring	Diagnosis, therapeutic intervention	Risk assessment, diagnosis, (individualized) therapeutic intervention	Risk assessment, diagnosis, disease monitoring, therapeutic intervention	Individualized therapeutic intervention
Example Tests	Panels that include cystic fibrosis, fragile X syndrome, sickle cell disease	Panels that include trisomies 13, 18, 21, and microdeletions	Cystic fibrosis	Whole genome sequencing (WGS) and whole exome sequencing (WES)	Comprehensive genomic profiling in NSCLC	Panel test for cardiovascular disease and diabetes risks	Panel tests for response to abacavir, warfarin, and carbamazepine
Possible Negative Consequences	Increased confusion and unwarranted anxiety (given variable penetrance, VUSs, especially with expanded panels)	Mistaken reliance on NIPT as diagnostic leads to terminations of unaffected fetuses; tests enter clinic without established PPVs	Newborn screening panels rapidly expand beyond AAP and ACMG recommendations; increased anxiety, confusion, and waste of resources	Patients and providers burdened with costs as payers refuse to cover, citing lack of evidence of clinical validity	Poor quality tests and unresolved technical challenges affecting tests lead to patient harm from therapeutic mismatches	Patients seek out interventions without established benefit, possibly with associated risks	Testing is costly but not does not lead to improved outcomes over standard of care
Possible Positive Consequences	Expanded screening lowers disease burden	NIPT as initial screen reduces exposure to risks of CVS and amniocentesis; expanded screening lowers disease burden	Appropriate expansion of newborn screening leads to improved outcomes	Catalyst for coverage policy innovation; leads to more effective therapeutic approaches, or precision medicine	Leads to more effective therapeutic approaches, or precision medicine	Patients are able to access effective interventions earlier, preventing disease or slowing disease progression	Ensures delivery of effective therapeutics and avoidance of toxicities, or precision medicine

NSCLC: non-small cell lung cancer, VUS: variant of uncertain significance, NIPT: non-invasive prenatal testing, PPV: positive predictive value, AAP: American Academy of Pediatrics, ACMG: American College of Medical Genetics, CVS: chorionic villus sampling