The ClinGen Gene Curation working group has developed a framework to standardize the approach to determine the clinical validity for a gene-disease pair. This framework:
- Defines the criteria needed to assess clinical validity
- Describes the evidence supporting a gene-disease association in a semi-quantitative manner, and
- Allows curators to use this information to methodically classify the validity of a given gene-disease pair.
This framework is currently optimized for genes associated with monogenic Mendelian disorders of reasonable penetrance. It is distinct from, and not meant to be a substitute for, the well-established statistical thresholds used for genome-wide association studies or validated methods to define multifactorial disease risk. Future iterations will expand the framework to consider the evaluation of oligogenic or multifactorial conditions.