Mitochondrial variant detection

Detection of variants in the mitochondrial genome with the DRAGEN small variant detection is outside the scope of ISO 15189 accreditation for the pipeline, but variants are provided to the user for consideration.

The detection algorithm utilises a continuous allele frequency model. Given that there are many copies of the mitochondrial genome per cell, the continuous allele frequency model is more appropriate for mitochondrial variant detection as it assumes that the variant allele fraction can vary between 0 – 100% and facilitates detection of low level heteroplasmy.

Please note that the measurement of uncertainty (i.e. the accuracy of heteroplasmy level value) was not determined against standard of care tests. The manufacturer’s (i.e. Illumina) stated limit of detection for mtDNA heteroplasmy is 1%, with recommended threshold of 2% to increase calling specificity (i.e. decrease the number of false positive calls), however these values have not been formally validated by Genomics England against standard of care tests.