bio-clinical-databases-tumor-mutational-burden

TMB Calculation from VCF (Ensembl VEP 111+)

Goal: Calculate tumor mutational burden as nonsynonymous coding mutations per megabase from a somatic VCF.

Approach: Iterate through VCF variants, filter for coding nonsynonymous consequences via VEP/SnpEff annotations, and divide count by panel size.

Panel-Specific TMB (Ensembl VEP 111+)

Goal: Calculate TMB normalized to known gene panel capture region sizes.

Approach: Look up the panel's megabase coverage from a reference table and pass to the TMB calculator.

## TMB with Variant Filtering (Ensembl VEP 111+)

**Goal:** Calculate TMB with quality and germline filters to reduce false positives.

**Approach:** Apply VAF, depth, and gnomAD population frequency filters before counting coding nonsynonymous variants.