Curation in ClinVar
Expert curation of variants
Expert curated variants are submitted to ClinVar by ClinGen-approved expert panels. Read more about expert panels in ClinVar.
NCBI staff do not curate variant classifications. Our staff work closely with submitters to ensure that each record submitted to ClinVar reflects the submitter’s assertion about the variant.
Problematic submitted records (SCVs)
Occasionally, a ClinVar user observes a submitted record (SCV) that appears to be incorrect or out of date. As an archive, ClinVar aims to represent the assertions made by our submitters; however, we also want to maintain the quality of the data in the database. For some of these error cases, the ClinVar team contacts submitters to request updates to submitted records (SCVs). However, submission to ClinVar, including maintenance of records by submitting updates, is voluntary and not all submitters are able to update their records upon request. This is particularly important when the problematic record causes a conflict in the overall classification of a variant.
For problematic SCV records that cannot be updated by the submitter, we have a process to flag the records, so that the records do not contribute to the overall variant classification. Because ClinVar is an archival database, flagged records remain in the database. Specific versions of SCV records are flagged, so if an SCV records is updated, the flag is removed and new version of the record is available for recuration, if applicable. This process of flagging problem records includes both manual curation performed by biocurators from the Clinical Genome Resource (ClinGen) and automated curation by NCBI staff.
Manual curation by ClinGen
A subset of ClinGen biocurators are trained to review SCV records in the ClinVar database. Priority is given to the review of conflicting entries in ClinVar; intralaboratory conflicts and P/LP vs VUS/LB/B conflicts are prioritized over VUS vs LB/B conflicts. SCV records may also be nominated by the community for review by ClinGen.
In their curation, the ClinGen biocurators identify records that are candidates for flagging in ClinVar. Common reasons include:
- Outlier claim with insufficient supporting evidence
- Claim with insufficient supporting evidence
- Conflicts with expert reviewed submission without evidence to support different classification
- Unnecessary conflicting claim for distinct condition when other classifications are more relevant
Read more about ClinGen’s curation process on their website.
The ClinGen biocurators send candidates for flagging to the ClinVar team on a monthly basis. The ClinVar team then emails each submitter with a candidate for flagging, including the reason the record was curated by ClinGen. Submitters have the option to update the record in ClinVar, but they are not required to. If the record is updated within 60 days, the record is not flagged in ClinVar. If an update within 60 days is not possible, the record is flagged in ClinVar so that it is still accessible but does not contribute to the overall classification.
Submitters who disagree with ClinGen’s curation are asked to reply with their rationale. You can email the ClinVar team at clinvar@ncbi.nlm.nih.gov and/or the ClinGen biocurators at clingen@clinicalgenome.org.
Automated curation by NCBI
Some errors can be identified automatically, without the need for manual curation. Currently we flag SCV records that appear to be redundant with a more recent SCV from the same submitter. Typically, it appears that the more recent record should have been an update to the previous record, but the more recent record was submitted as new. These cases include:
- One SCV where no condition is provided (either “not provided” or “not specified”) and another SCV where a condition is provided
- Both SCVs have no condition provided (either “not provided” or “not specified”)
Submitters with records flagged for being redundant can choose to clean up the flagged records by merging them with the more recent records. Read our instructions for merging records in a ClinVar submission, or contact us at clinvar@ncbi.nlm.nih.gov for assistance.