About Gene-Disease Clinical Validity Curation

Does variation in this gene cause disease?

ClinGen Gene-Disease Clinical Validity curation attempts to answer this question. The curation process (usually abbreviated to "gene curation") involves evaluating the strength of evidence supporting or refuting a claim that variation in a particular gene causes a particular disease. The final result of gene curation is a classification of the gene-disease pair into one of five categories depending on the strength of evidence:

• No Known Disease Relationship

• Limited

• Moderate

• Strong

• Definitive

Gene-disease clinical validity curation is led by gene curators from ClinGen Gene Curation Expert Panels (GCEPs). Curators first perform a pre-curation literature search to gather pertinent data from published articles. An important next step is to assign the correct disease (using MONDO disease ontology) by following the lumping and splitting criteria. This disease information must be curated into the ClinGen Gene Tracker tool prior to starting gene curation for each gene-disease pair.

​The gene curation process is performed in the Gene Curation Interface (GCI) and is restricted to curators who are affiliated with a GCEP. A gene-disease record is often referred to as a "GDM" - short for "Gene-Disease-Mode of Inheritance", the three required components of the record. Within each gene-disease record, the genetic and experimental evidence gathered from publications is evaluated and scored according to the gene-disease clinical validity classification framework that was developed by the ClinGen Gene Curation Working Group. The GCI assists curators by collating all the scored evidence and providing a calculated classification, but if required GCEPs can modify their classification. Once the GCEP has finalized their classification selection, they can provisionally save it, and pass it along for their expert review process. Upon successful review, the GCEP can approve their final classification and publish it to the ClinGen website.

A visual representation of the full gene curation workflow is shown below.

For more information about ClinGen gene curation, please check out the information on the https://clinicalgenome.org/curation-activities/gene-disease-validity/ website or get in touch with the Gene Curation working group at genecuration@clinicalgenome.org.