The summary reports provide information on gene-condition pairs that meet a clinical actionability threshold for pathogenic variants in the gene, and are prepared using a transparent, systematic, evidence-based process. A protocol guides the summary development, which includes quality rating of the evidence. An expert panel reviews the summaries and applies a semi-quantitative metric (SQM) to score the overall clinical actionability of gene variants discovered incidental to another diagnostic investigation. For scoring, specific intervention-outcome pairs are chosen for each genetic disorder under consideration. Clinical interventions are chosen based on their effectiveness for prevention or delay of clinical disease, lowered clinical burden, or improved clinical outcomes in a previously undiagnosed adult. If you adapt or utilize the actionability curation procedure, semi-quantitative metric, or summary reports, please cite:

Hunter JE, Irving SA, Biesecker LG, Buchanan A, Jensen B, Lee K, Martin CL, Milko L, Muessig K, Niehaus AD, O’Daniel J, Piper MA, Ramos EM, Schully SD, Scott AF, Slavotinek A, Sobreira A, Strande N, Weaver M, Webber EM, Williams MS, Berg JS, Evans JP, Goddard KAB, on behalf of the ClinGen Resource. A standardized, evidence-based protocol to assess clinical actionability of genetic disorders associated with genomic variation. Genet Med 2016 Apr 28. PMCID: PMC5085884

Semi-quantitative Metric (SQM)

Category

Levels

Level of Evidence

Severity

3 - sudden death

2 - possible death or major morbidity

1 - modest morbidity

0 - minimal or no morbidity

NA

Likelihood of Disease

3 - >40% chance

2 - 5-39% chance

1 - 1-4% chance

0 - <1% chance or unknown

A = substantial evidence

B = moderate evidence

C = minimal evidence

D = poor evidence

N = non-systematically identified or expert contributed evidence

Effectiveness

3 - highly effective
2 - moderately effective
1 - minimally effective

0 - ineffective/no intervention

IN* - ineffective/no intervention

A = substantial evidence

B = moderate evidence

C = minimal evidence

D = poor or conflicting evidence

N = non-systematically identified or expert contributed evidence

Nature of Intervention

3 - low risk/medically acceptable/ low intensity intervention

2 - moderately acceptable/risk/ intensive interventions

1 - greater risk/less acceptable/ substantial interventions

0 - high risk/poor acceptable/ intensive or no intervention

NA

 

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View and export all Adult Actionability Working Group consensus scores for outcome-intervention pairs in a customizable, searchable interface.

View and export all Pediatric Actionability Working Group consensus scores for outcome-intervention pairs in a customizable, searchable interface.