Clinotator

Clinotator extracts and synthesizes ClinVar evidence to score and prioritize clinical genetic variants for interpretation.

Key Features:

• Batch Processing: Processes large batches of variants from lists of ClinVar Variation IDs or dbSNP rsIDs and from annotated VCF files, supporting datasets on the order of 15,000–50,000 variants.
• Criteria-Based Clinical Assertions Extraction: Extracts criteria-based clinical assertions from ClinVar with emphasis on the strength and consistency of evidence for clinical significance.
• Weighted Metrics Generation: Computes weighted metrics including the Clinotator Raw Score, Average Clinical Assertion Age, Clinotator Predicted Significance, and Eclassification Recommendation.
• Filtering Mechanism: Weights clinical assertions by significance type, age of submission, and submitter expertise category to filter and prioritize assertions.
• Prioritization of Discordant Variants: Identifies and prioritizes variants with discordant or outdated assertions for potential reclassification.

Scientific Applications:

• Variant Curation: Supports curation workflows by identifying assertions in ClinVar that require update or re-evaluation.
• Research Insights: Provides metrics to assess variant pathogenicity trends and to analyze patterns of discordance within ClinVar datasets.

Methodology:

Queries NCBI eutilities to retrieve ClinVar Variation Reports and computes ClinVar Variation Report scoring metrics.