clinvar-database

What it does

Guides an agent to query ClinVar using E-utilities to obtain clinical significance classifications, pathogenicity, and disease associations for specified variants. It supports searches by gene, rsID, or condition, and can retrieve summary records, full XML records, and bulk ClinVar data. It also includes workflows to map variants to conditions and to filter by review status.

How it works

• Use ESearch to find ClinVar Variation IDs by a structured query (gene, rsID, or condition, with optional clinsig filters).
• Use ESummary to fetch structured summary data for a list of Variation IDs, extracting ClinVar classifications, review status, gene symbols, and trait information.
• Use EFETCH with rettype=vcv and is_variationid=true to fetch full XML records (VariationArchive) for detailed submitter and condition data.
• Use FTP bulk data via variant_summary.txt.gz for large-scale queries, streaming the file and filtering for pathogenic/related entries.
• Use specific examples to map variation IDs to conditions via germline_classification trait_set or equivalent fields, and to examine review status levels.
• Provide guidance on combining rsIDs with searches, and on how to interpret review status stars (0–4).

When to use it

• When you need to check clinical significance for a variant (rsID, HGVS, or genomic position).
• When you want to retrieve all pathogenic/likely pathogenic variants in a gene, or explore conflicting interpretations.
• When you need condition/phenotype associations for a variant or to build variant filtering pipelines that prioritize clinically actionable variants.
• When dealing with somatic cancer variants, or when you need GWAS associations via separate databases.

What it can touch

• Uses tools and endpoints provided by NCBI E-utilities (esearch.fcgi, esummary.fcgi, efetch.fcgi).
• Interacts with ClinVar data via the eutils API, and, for bulk data, with the ClinVar FTP: ftp.ncbi.nlm.nih.gov/pub/clinvar/tab_delimited/variant_summary.txt.gz

Caveats

• Requires a valid email parameter for rate-limiting and policy compliance; rate limits: 3 requests/second unauthenticated, 10/second with API key.
• ClinVar’s data schema in 2024 may present germline_classification and trait_set structures in esummary results; adapt parsing accordingly.
• The XML fetch via rettype=vcv with is_variationid=true yields VariationArchive records; older clinvarset formats may differ.
• For very large queries, prefer the FTP bulk download over repeated ES calls to avoid rate limits.