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.

Publication

Read the publication describing the ClinGen gene-disease validity evaluation process.

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Clinical Validity Classifications

The Clinical Validity Classifications are used to qualitatively describe the strength of evidence documenting a gene-disease association.  Note: these terms do not reflect the effect size or relative risk attributable to variants in a particular gene.

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Genetic Evidence Scoring Metric

Scoring metric to guide curators in assessing genetic evidence.  

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Experimental Evidence Scoring Metric

Scoring metric to guide curators in assessing experimental evidence.

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Summary Scoring Metric

Once genetic and experimental evidence has been assessed, this summary scoring metric can be used to arrive a clinical validity classification.

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Supplemental Methods for Validation

Brief description of how the gene-disease pairs in the original publication were validated.

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