Documentation / Variant Analysis / Mitochondrial Variants
Mitochondrial Variant Analysis
Mitochondrial variants are not evaluated by the nuclear sequence-variant path. Folklore uses a dedicated mtDNA framework based on the Mitochondrial Disease Working Group specifications described by McCormick et al. (2020).
Why mtDNA Is Separate
Heteroplasmy
The proportion of mitochondrial genomes carrying a variant can differ across samples and tissues.
Maternal inheritance
Inheritance and segregation require mitochondrial rather than autosomal interpretation.
Haplogroup context
Population lineage context can change how a common or haplogroup-defining variant is interpreted.
Different evidence sources
mtDNA-specific population, clinical, functional, and computational resources are used where available.
Evidence and Output
The mtDNA path evaluates the subset of criteria that can be applied responsibly to mitochondrial variants, records mtDNA-specific provenance, and excludes nuclear criteria that do not translate to mitochondrial biology. Evidence that depends on functional studies, maternal segregation, tissue heteroplasmy, or expert curation remains visible as a review boundary rather than being inferred.
The result uses the familiar five-tier terminology, but its evidence trace identifies the mitochondrial framework. A nuclear and a mitochondrial result should not be interpreted as if they were produced by the same criteria set.
Clinical limitation
Blood heteroplasmy may not represent an affected tissue, and a computational result cannot establish tissue distribution, threshold effect, or causality. Review should include phenotype, maternal history, sample type, heteroplasmy, and relevant functional evidence.
Reference: McCormick EM, et al. Human Mutation. 2020;41(12):2028-2057. PMID: 33058415