InterVar

InterVar automates application of ACMG/AMP criteria to classify the clinical significance of human genetic variants for disease interpretation.

Key Features:

• ACMG/AMP criteria automation: Automates application of 18 of the 28 ACMG/AMP evidence criteria for variant classification.
• Input formats: Accepts pre-annotated input files or Variant Call Format (VCF) files.
• Guideline-aligned classifications: Generates automated variant interpretations aligned with ACMG/AMP clinical guidelines.
• Companion wInterVar web server: Provides the automated interpretation step with an option for manual adjustment of results.
• Validated in sequencing studies: Demonstrated in published sequencing studies to reduce the time required for clinical variant interpretation.

Scientific Applications:

• Clinical variant interpretation: Supports classification of the clinical significance of sequence variants in human genetic disease.
• Severe congenital and early-onset developmental disorders: Applied to investigate severe congenital disorders and very early-onset developmental conditions characterized by high penetrance.
• Standardization across studies: Promotes more consistent and efficient variant classification by standardizing the application of ACMG/AMP criteria.

Methodology:

Applies 18 of 28 ACMG/AMP criteria to pre-annotated or Variant Call Format (VCF) inputs to produce automated ACMG/AMP-aligned variant classifications; the wInterVar web server implements the automated interpretation step and permits manual adjustment of results.