ClinVar Database

Prerequisites

1. uv: Read the uv skill and follow its Setup instructions to ensure uv is installed and on PATH.
2. User Notification: If .licenses/clinvar_database_LICENSE.txt does not already exist in the workspace root directory then (1) prominently notify the user to check the terms at https://www.ncbi.nlm.nih.gov/clinvar/, then (2) create the file recording the notification text and timestamp.
3. .env file: Make sure the .env file exists in your home directory. Create one if it does not exist.
4. NCBI_API_KEY (optional): Raises the NCBI rate limit from 3 to 10 requests/second. The skill works without it, but a key is recommended if the user plans many queries or encounters a 429 error. You can register for a key for free at https://www.ncbi.nlm.nih.gov/account/settings/. You MUST use the safe credentials protocol in the credentials skill to check for and request this key if this skill looks relevant to the user's request.

Overview

ClinVar is the primary consensus record for clinical classifications of human genomic variations. It provides the "clinical ground truth" for pathogenicity labels (Pathogenic, Likely Pathogenic, Benign, VUS) based on assertions from global laboratories.

When to Use

Use when you need to:

• Find the current clinical significance and star rating (review status) for a specific variant.
• Fetch clinician notes, assertion criteria, or rationales for previous clinical laboratory classifications.
• Retrieve the preferred condition name and associated HPO terms for a specific variant.
• Find a list of variant controls (e.g., "Find all Pathogenic variants in the HBB gene within 50bp of a signal").
• Check for conflicting interpretations for a given variant and identify the organizations submitting each classification.

Do NOT use when you need to: