Variant Analysis
Folklore turns normalized variant records into a reviewable clinical evidence summary. It annotates each supported variant, assigns the appropriate interpretation framework, evaluates available evidence, and records the framework, evidence codes, and resulting class.
The automated result is decision support, not a diagnosis. Patient phenotype, inheritance, family evidence, assay quality, and expert review remain essential to clinical interpretation.
Framework Selection
Nuclear sequence variants
Evaluated with the ACMG/AMP evidence framework, ClinGen guidance, and applicable gene-specific VCEP specifications.
Mitochondrial variants
Evaluated separately with mtDNA-specific specifications that account for heteroplasmy, haplogroups, and mitochondrial population evidence.
Structural variants
Constitutional copy-number loss and gain use the ClinGen/ACMG Riggs 2020 framework. Other eligible nuclear structural events can use the nuclear variant framework; unsupported records remain explicitly unclassified.
What the Result Contains
Five-tier class
Pathogenic, Likely Pathogenic, VUS, Likely Benign, or Benign when a supported framework reaches a result.
Evidence trace
The criteria and strength modifiers that contributed to the automated result.
Framework provenance
The nuclear, mitochondrial, or structural framework that owned the interpretation.
Review context
Warnings, source markers, and any geneticist reclassification remain visible alongside the pipeline result.
In This Section
ACMG/AMP Framework
The evidence model used for nuclear sequence variants.
Criteria Reference
A clinical-level guide to the 28 ACMG/AMP evidence codes.
Combining Rules
How evidence strengths are combined into the five-tier result.
ClinVar and ClinGen
How external assertions enter the evidence and decision paths.
Conflicting Evidence
How contradictory evidence is held for safe review.
Confidence Indicator
What the displayed class-level indicator means and does not mean.
Mitochondrial Variants
The dedicated mtDNA interpretation framework and its boundaries.
Review and Reclassification
How a geneticist can record, audit, and revert a reviewed class.