Table 1.

Level of actionability of the molecular variants.

TIER 1 Variants of Strong Clinical Significance	TIER 2 Variants of Potential Clinical Significance	TIER 3 Variants of Unknown Clinical Significance	TIER 4 Benign or Likely Benign Variants
Therapeutic, Prognostic, and Diagnostic Value	Therapeutic, Prognostic, and Diagnostic Value
Level A evidence FDA approved therapy included in guidelines	Level C evidence FDA-approved therapies for different tumor types or investigational therapies Multiple small, published studies with consensus	Not observed at a significant allele frequency in the general or specific subpopulation databases or pan-cancer or tumor-specific variant databases No convincing published evidence or cancer association	Observed at significance allele frequency in the general or specific subpopulation databases No existing published evidence of cancer association
Level B evidence Well-powered studies with consensus from experts in the field	Level D evidence Preclinical trials or case reports without consensus