Cardiac heteroplasmy needs a tissue denominator

A cardiac disease framework and a multisystem mitochondrial case can assign different meaning to the same heteroplasmy estimate. Blood may be the available specimen, while myocardium or another affected tissue may carry a different variant fraction because of tissue distribution, age, and cell composition.

For claims linking heteroplasmy to cardiac disease, the evidence should identify the assayed tissue, heteroplasmy denominator, detection limit, sampling age, and whether cardiac involvement was compared with matched blood or other affected tissue. The m.10010T>C case is especially relevant if its hypoparathyroid and other manifestations were assessed against specimen-specific measurements rather than one systemic estimate. Discordance between phenotype and accessible-tissue heteroplasmy could reflect tissue segregation, threshold assumptions, or an incomplete genotype to phenotype model.