Table 2. Semi-quantitative metric to score clinical actionability.

Domain	Scores
Severity: What is the nature of the threat to health to an individual carrying a clearly deleterious allele in this gene?	3 = Reasonable possibility of sudden death
	2 = Reasonable possibility of death or major morbidity
	1 = Modest morbidity
	0 = Minimal or no morbidity
Likelihood of disease: What is the chance that a serious outcome will materialize given a deleterious variant (akin to penetrance)?	3 = >40% chance
	2 = 5–39% chance
	1 = 1–4% chance
	0 = <1% chance
Effectiveness of specific interventions: How effective is the selected, specific intervention for preventing or significantly diminishing the risk of harm?	3 = Highly effective
	2 = Moderately effective
	1 = Minimally effective
	0 = Controversial or unknown effectiveness
	IN = Ineffective/No interventiona
Nature of intervention: How risky, medically burdensome, or intensive is a given intervention?	3 = Low risk, or medically acceptable and low-intensity interventions
	2 = Moderate risk, moderately acceptable or intensive interventions
	1 = Greater risk, less acceptable and substantial interventions
	0 = High risk, poorly acceptable or intensive interventions
State of the knowledge base: What is the level of evidence?	A = Substantial evidence, or evidence from a high tier (Tier 1)
	B = Moderate evidence, or evidence from a moderate tier (Tier 2)
	C = Minimal evidence, or evidence from a lower tier (Tier 3 or 4)
	D = Poor evidence, or evidence not provided in the report
	E = Evidence based on expert contributions (Tier 5)

^aDo not score the remaining categories.