Table 1.

Criteria for Stages I & II

Stage I
Criteria	Questions
Actionability	Is there a practice guideline or systematic review for the genetic condition?
	Does the practice guideline or systematic review indicate that the result is actionable in one or more of the following ways: a) patient management, b) surveillance or screening, c) family management, or d) circumstances to avoid?
	Is the result actionable in an undiagnosed adult with the genetic condition?
Penetrance	Is there at least one known pathogenic variant with at least moderate penetrance (≥40%) or moderate relative risk (≥2) for important health implications in any population?
Significance/Burden of disease	Is this condition an important health problem?
Stage II
Criteria	Questions
Significance/Burden of disease	What is the nature of the threat to health for an individual carrying a deleterious allele?
	Disease Incidence	Disease Prevalence
	Clinical Features (Signs/Symptoms)	Natural History
	Significance/Burden of Condition
Actionability	How effective are available interventions for preventing the harm?
	Patient Management	Surveillance
	Family Management	Circumstances to Avoid
Penetrance	What is the chance that this threat will materialize?
	Prevalence	Penetrance
	Expressivity	Relative Risk
Acceptability of Intervention	How acceptable are available interventions in terms of the burdens or risks placed on the individual?
Risks	Would the underlying risk or condition escape detection prior to harm in the setting of recommended care?
	Chance to escape clinical detection in adults