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) |
Do not score the remaining categories.