ClinVar is a free public archive (funded by the NIH) of human genotype to phenotype relationships along with supporting evidence. Data can be submitted by various entities including clinical testing labs, researchers, and expert panels. ClinGen is another NIH supported resource that defines the clinical relevance of genes and variants for use in precision medicine and research. It has a strong partnership with ClinVar and both work to increase data sharing and collaborative curation to characterize and disseminate the clinical relevance of genomic variation.
Data in ClinVar is not curated and hence can have discordance across the submissions. A variant submitted by one lab may have a different classification from the same variant submitted by a different lab. ClinGen and ClinVar have worked together to improve the quality of submisions in ClinVar and encourage all labs to submit their data and interpretations. One system they have implemented to indicate the relevance of the clinical significance is the 4-star rating to indicate the level of review (Review Status) supporting the assertion of clinical relevance. For example, if no submission criteria is provided, the Review Status for the variant has no stars. If the variant was from a single submitter with assertion criteria, it gets one star. If there are two or more submitters with assertion criteria and with the same interpretation, the variant gets two stars. Three stars indicates review by a group with the “expert panel” designation and four stars indicates review by a group with “practice guideline” designation.
To further enhance quality assurance, the group now puts forth a list of clinical laboratories that meet minimum requirements for data sharing. Requirements to make this list are registration in ClinVar with single star Review Status, registration in the Genetic Test Registry with yearly review, lab has submitted at least 100 variants, lab submits at least one variant a year and updates reclassified variants as necessary, lab submits all categories of variants returned to patients, attests to submitting at least 75% of all variants reported in the past year, and CLIA certification.
In addition to membership in this list, labs can also earn badges for additional achievements (based on self-reported data) such as actively working to resolve interlab interpretation differences or for having a majority of submissions with evidence submitted. Currently there are 10 labs on the list and each has earned at least one badge. I am also pleased to see that two of the labs on the list use BioDiscovery’s NxClincial software solution for integrated CNV, AOH, and Sequence Variant review and reporting. In the upcoming version of NxClinical many new features will be added to further support the integrated ClinVar data and provide users a level of assurance for the variant classifications.
