Table 1:
ClinGen Actionability Working Group semi-quantitative score metric (Originally published in Hunter et, 2016, scoring metric adapted from Berg et al, 2016)
| 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 intervention† |
| 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.
‡ Tier 1: Evidence from a systematic review/meta-analysis or a clinical practice guideline clearly based on a systematic review; Tier 2: Evidence from clinical practice guidelines using expert consensus; Tiers 3 and 4: Evidence from a non-systematic review of evidence with additional primary literature cited (Tier 3) or not cited (Tier 4); Tier 5: Expert contribution or non-systematically identified evidence.