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HelpMayo Test ID MITOP Mitochondrial Full Genome Analysis, Next-Generation Sequencing (NGS), Varies
Ordering Guidance
If testing for variants in the mitochondrial genes encoded by the nuclear genome is requested, order NMITO / Nuclear Mitochondrial Gene Panel, Next-Generation Sequencing, Varies. Alternatively, order CMITO / Combined Mitochondrial Full Genome and Nuclear Gene Panel, Varies for both the mitochondrial genome and mitochondrial genes encoded by the nuclear genome.
Additional Testing Requirements
For cord blood specimens: Maternal cell contamination (MCC) studies are available. Order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on both the cord blood and maternal specimens under separate order numbers. Cord blood testing will proceed without MCC studies, but results may be compromised if MCC is present.
Necessary Information
Molecular Genetics: Biochemical Disorders Patient Information (T527) is available to provide information useful for accurate test interpretation. At minimum, provide a reason for testing with each specimen. Although testing may proceed without this information, ordering healthcare professionals are strongly encouraged to complete the form and send it with the specimen.
Specimen Required
Patient Preparation: A previous hematopoietic stem cell transplant from an allogenic donor will interfere with testing. For information about testing patients who have received a hematopoietic stem cell transplant, call 800-533-1710.
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Container/Tube:
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Green top (Sodium heparin)
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient 4 days/Refrigerated 4 days/Frozen 4 days
Additional Information:
1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for specimens received after 4 days, and DNA yield will be evaluated to determine if testing may proceed.
2. To ensure minimum volume and concentration of DNA are met, the requested volume must be submitted. Testing may be canceled if DNA requirements are inadequate.
Specimen Type: Cord blood
Container/Tube:
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Green top (Sodium heparin)
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send cord blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 4 days/Frozen 4 days
Additional Information:
1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for specimens received after 4 days, and DNA yield will be evaluated to determine if testing may proceed.
2. To ensure minimum volume and concentration of DNA are met, the requested volume must be submitted. Testing may be canceled if DNA requirements are inadequate.
3. While a properly collected cord blood sample may not be at risk for maternal cell contamination, unanticipated complications may occur during collection. Therefore, maternal cell contamination studies are recommended to ensure the test results reflect that of the patient tested and are available at an additional charge. Order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Specimen Type: Saliva
Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.
Supplies: Saliva Swab Collection Kit (T786)
Specimen Volume: 2 Swabs
Collection Instructions: Collect and send specimen per kit instructions.
Specimen Stability Information: Ambient (preferred) 30 days/Refrigerated 30 days
Additional Information: Saliva specimens are acceptable but not recommended. Due to lower quantity/quality of DNA yielded from saliva, some aspects of the test may not perform as well as DNA extracted from a whole blood sample. When applicable, specific gene regions that were unable to be interrogated will be noted in the report. Alternatively, additional specimen may be required to complete testing.
Specimen Type: Skin biopsy
Supplies: Fibroblast Biopsy Transport Media (T115)
Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin.
Specimen Volume: 4-mm Punch
Specimen Stability Information: Ambient (preferred) <24 hours/Refrigerated <24 hours
Additional Information:
1. Specimens are preferred to be received within 24 hours of collection. Culture and extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.
2. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks are required to culture fibroblasts before genetic testing can occur.
Specimen Type: Cultured fibroblasts
Source: Skin
Container/Tube: T-25 flask
Specimen Volume: 2 Flasks
Collection Instructions: Submit confluent cultured fibroblast cells from a tissue biopsy.
Specimen Stability Information: Ambient (preferred) <24 hours/Refrigerated <24 hours
Additional Information:
1. Specimens are preferred to be received within 24 hours of collection. Culture and extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.
2. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks are required to culture fibroblasts before genetic testing can occur.
Specimen Type: Tissue biopsy
Supplies: Hank's Solution (T132)
Container/Tube: Sterile container with sterile Hank's balanced salt solution, Ringer's solution, or normal saline
Specimen Volume: 0.5 to 3 cm(3) or larger
Specimen Stability Information: Ambient (preferred) <24 hours/Refrigerated <24 hours
Additional Information:
1. Specimens are preferred to be received within 24 hours of collection. Culture and extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.
2. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks are required to culture fibroblasts before genetic testing can occur
Specimen Type: Snap frozen nerve tissue biopsy
Collection Instructions: Prepare snap frozen tissue biopsy per surgical procedure
Specimen Volume: 0.25 to 0.5 cm
Specimen Stability Information: Frozen
Specimen Type: Muscle tissue biopsy
Supplies: Muscle Biopsy Kit (T541)
Specimen Volume: 20 to 80 mg
Collection Instructions: Prepare and transport specimen per instructions in Muscle Biopsy Specimen Preparation.
Specimen Stability Information: Frozen (preferred) <24 hours/Ambient <24 hours/Refrigerated <24 hours
Additional Information: Specimens are preferred to be received within 24 hours of collection. Extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.
Specimen Type: Blood spot
Supplies: Card-Blood Spot Collection (Filter Paper) (T493)
Container/Tube:
Preferred: Collection card (Whatman Protein Saver 903 Paper)
Acceptable: PerkinElmer 226 filter paper or blood spot collection card
Specimen Volume: 2 to 5 Blood spots
Collection Instructions:
1. An alternative blood collection option for a patient older than 1 year is a fingerstick. For detailed instructions, see How to Collect a Dried Blood Spot Sample.
2. Let blood dry on the filter paper at ambient temperature in a horizontal position for a minimum of 3 hours.
3. Do not expose specimen to heat or direct sunlight.
4. Do not stack wet specimens.
5. Keep specimen dry
Specimen Stability Information: Ambient (preferred)/Refrigerated
Additional Information:
1. Blood spot specimens are acceptable but not recommended. Multiple extractions will be required to obtain sufficient yield for supplemental analysis, and there is significant risk for test failure due to insufficient DNA.
2. Due to lower concentration of DNA yielded from blood spot, some aspects of the test may not perform as well as DNA extracted from a whole blood sample. When applicable, specific gene regions that were unable to be interrogated will be noted in the report. Alternatively, additional specimen may be required to complete testing.
3. For collection instructions, see Blood Spot Collection Instructions
4. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777)
5. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800)
Specimen Type: Extracted DNA
Container/Tube:
Preferred: Screw Cap Micro Tube, 2 mL with skirted conical base
Acceptable: Matrix tube, 1 mL
Collection Instructions:
1. The preferred volume is at least 100 mcL at a concentration of 75 ng/mcL.
2. Include concentration and volume on tube.
Specimen Stability Information: Frozen (preferred) 1 year/Ambient/Refrigerated
Additional Information: DNA must be extracted in a CLIA-certified laboratory or equivalent and must be extracted from a specimen type listed as acceptable for this test (including applicable anticoagulants). Our laboratory has experience with Chemagic, Puregene, Autopure, MagnaPure, and EZ1 extraction platforms and cannot guarantee that all extraction methods are compatible with this test. If testing fails, one repeat will be attempted, and if unsuccessful, the test will be reported as failed and a charge will be applied. If applicable, specific gene regions that were unable to be interrogated due to DNA quality will be noted in the report.
PRENATAL SPECIMENS
Due to its complexity, consultation with the laboratory is required for all prenatal testing; call 800-533-1710 to speak to a genetic counselor.
Specimen Type: Amniotic fluid
Container/Tube: Amniotic fluid container
Specimen Volume: 20 mL
Specimen Stability Information: Ambient (preferred) <24 hours/Refrigerated <24 hours
Additional Information: Specimen will only be tested after culture.
1. Specimens are preferred to be received within 24 hours of collection. Culture and extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.
2. A separate culture charge will be assessed under CULAF / Culture for Genetic Testing, Amniotic Fluid. An additional 2 to 3 weeks are required to culture amniotic fluid before genetic testing can occur.
3. All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Specimen Type: Confluent cultured amniocytes
Container/Tube: T-25 flask
Specimen Volume: 2 Full flasks
Collection Instructions: Submit confluent cultured amniocytes from another laboratory
Specimen Stability Information: Ambient (preferred) <24 hours/Refrigerated <24 hours
Additional Information:
1. Specimens are preferred to be received within 24 hours of collection. Culture and extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.
2. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing.
3. All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Specimen Type: Chorionic villi
Container/Tube: 15-mL tube containing 15 mL of transport media
Specimen Volume: 20 mg
Specimen Stability Information: Ambient (preferred) <24 hours/Refrigerated <24 hours
Additional Information: Specimen will only be tested after culture.
1. Specimens are preferred to be received within 24 hours of collection. Culture and extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.
2. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.
3. All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Specimen Type: Cultured chorionic villi
Container/Tube: T-25 flasks
Specimen Volume: 2 Full flasks
Collection Instructions: Submit confluent cultured cells from another laboratory
Specimen Stability Information: Ambient (preferred) <24 hours/Refrigerated <24 hours
Additional Information:
1. Specimens are preferred to be received within 24 hours of collection. Culture and extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.
2. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing.
3. All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Useful For
Diagnosis of the subset of mitochondrial diseases that result from variants in the mitochondrial genome
A second-tier test for patients in whom previous targeted gene variant analyses for specific mitochondrial disease-related genes were negative
Identifying variants within genes of the mitochondrial genome that are known to be associated with mitochondrial disease, allowing for predictive testing of at-risk family members
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| CULFB | Fibroblast Culture for Genetic Test | Yes | No |
| CULAF | Amniotic Fluid Culture/Genetic Test | Yes | No |
| MATCC | Maternal Cell Contamination, B | Yes | No |
Testing Algorithm
Skin biopsy:
If skin biopsy is received, fibroblast culture will be added at an additional charge. If viable cells are not obtained, the client will be notified.
Prenatal specimens:
If an amniotic fluid specimen is received, an amniotic fluid culture will be performed at an additional charge.
If chorionic villi, cultured chorionic villi, or cultured amniocyte specimen is received, a fibroblast culture will be performed at an additional charge.
For any prenatal specimen that is received, maternal cell contamination testing will be performed at an additional charge.
Cord blood:
For cord blood specimens that have an accompanying maternal blood specimen, maternal cell contamination studies will be performed at an additional charge.
The following algorithms are available:
-Epilepsy: Unexplained Refractory and/or Familial Testing Algorithm
Special Instructions
- Muscle Biopsy Specimen Preparation Instructions
- Molecular Genetics: Biochemical Disorders Patient Information
- Informed Consent for Genetic Testing
- Blood Spot Collection Card-Spanish Instructions
- Blood Spot Collection Card-Chinese Instructions
- Epilepsy: Unexplained Refractory and/or Familial Testing Algorithm
- Neuromuscular Myopathy Testing Algorithm
- Informed Consent for Genetic Testing (Spanish)
- Blood Spot Collection Instructions
Method Name
Long-Range Polymerase Chain Reaction (LR-PCR) followed by Next-Generation Sequencing (NGS) and Droplet Digital Polymerase Chain Reaction (ddPCR) as needed
Reporting Name
Mitochondrial Full Genome AnalysisSpecimen Type
VariesSpecimen Minimum Volume
See Specimen Required
Specimen Stability Information
| Specimen Type | Temperature | Time |
|---|---|---|
| Varies | Varies | |
Reject Due To
All specimens will be evaluated by at Mayo Clinic Laboratories for test suitability.Clinical Information
The mitochondrion occupies a unique position in eukaryotic biology. It is the site of energy metabolism, and it is the sole subcellular organelle composed of proteins derived from 2 genomes, mitochondrial and nuclear. A group of hereditary disorders due to variants in either the mitochondrial genome or nuclear mitochondrial genes have been well characterized.
The diagnosis of mitochondrial disease can be particularly challenging as the presentation can occur at any age, involve virtually any organ system, and be associated with widely varying severities. This test utilizes massively parallel sequencing, also termed next-generation sequencing (NGS), to determine the exact sequence of the entire 16,569 base-pair mitochondrial genome.
The utility of this test is to assist in the diagnosis of the subset of mitochondrial diseases that result from variants in the mitochondrial genome. This includes certain types of myopathies and neuro-ophthalmologic diseases, such as MELAS (mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes), MERRF (myoclonic epilepsy with ragged red fibers), mitochondrial myopathy, neurogenic muscle weakness, ataxia, retinitis pigmentosa, Leigh syndrome, Leber hereditary optic neuropathy, and chronic progressive external ophthalmoplegia. In addition to the detection of single base changes with these disorders, large deletions, such as those associated with Kearns-Sayre or Pearson syndromes, are also detected. Variants in mitochondrial proteins encoded by genes in the nucleus, such as the enzymes of fatty acid oxidation, are not detected using this test.
In contrast to variants in nuclear genes, which are present in either 0, 1, or 2 copies, mitochondrial variants can be present in any fraction of the total organelles, a phenomenon known as heteroplasmy. Typically, the severity of disease presentation is a function of the degree of heteroplasmy. Individuals with a higher fraction of altered mitochondria present with more severe disease than those with lower percentages of altered alleles. The sensitivity for the detection of altered alleles in a background of wild-type (or normal) mitochondrial sequences by NGS is approximately 10%.
Reference Values
An interpretive report will be provided.
Interpretation
All detected variants are evaluated according to American College of Medical Genetics and Genomics guidelines for mitochondrial DNA variant interpretation.(1) Other gene-specific guidelines may also be considered. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance. The degree of heteroplasmy of each single nucleotide or delin (deletion-insertion) variant, defined as the ratio (percentage) of variant sequence reads to the total number of reads, will also be reported. Variants detected at or above 95% will be reported as homoplasmic. Heteroplasmy for large deletions will be reported and is determined by droplet digital polymerase chain reaction. Variants classified as benign or likely benign are not reported.
Cautions
Clinical Correlations:
A small percentage of individuals who have mitochondrial genome involvement may have a variant that is not identified by the methods performed. The absence of a variant, therefore, does not eliminate the possibility of a mitochondrial disease due to variant in the mitochondrial genome. Variants in mitochondrial genes encoded by the nuclear genome will not be detected with this assay. For predictive testing of asymptomatic individuals, it is important to first document the presence of a gene variant in an affected family member.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.
Technical Limitations:
In some cases, DNA variants of undetermined significance may be identified.
Rare variants (ie, polymorphisms) exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.
Evaluation Tools:
Multiple in-silico evaluation tools were used to assist in the interpretation of these results. These tools are updated regularly; therefore, changes to these algorithms may result in different predictions for a given variant. Additionally, the predictability of these tools for the determination of pathogenicity is currently unvalidated.
Unless reported or predicted to cause disease, variants in protein coding genes that do not result in an amino acid substitution are not reported. These and common variants identified for this patient are available upon request.
Reclassification of Variants-Policy:
Currently, it is not standard practice for the laboratory to systematically review previously classified variants on a regular basis. The laboratory encourages healthcare professionals to contact the laboratory at any time to learn how the classification of a particular variant may have changed over time. Due to broadening genetic knowledge, it is possible that the laboratory may discover new information of relevance to the patient. Should that occur, the laboratory may issue an amended report.
Clinical Reference
1. McCormick EM, Lott MT, Dulik MC, et al. Specifications of the ACMG/AMP standards and guidelines for mitochondrial DNA variant interpretation. Hum Mutat. 2020;41(12):2028-2057
2. Munnich A, Rotig A, Cormier-Daire V, Rustin P. Clinical presentation of respiratory chain deficiency. In: Valle D, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA, eds. The Online Metabolic and Molecular Basis of Inherited Disease. McGraw-Hill; 2019. Accessed June 16, 2025. Available at https://ommbid.mhmedical.com/content.aspx?bookid=2709§ionid=225086827
3. Wallace DC, Lott MT, Brown MD, Kerstann K. Mitochondria and neuro-ophthalmologic diseases. In: Valle D, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA, eds. The Online Metabolic and Molecular Basis of Inherited Disease. McGraw-Hill; 2019. Accessed June 16, 2025. Available at https://ommbid.mhmedical.com/content.aspx?bookid=2709§ionid=225088522
4. Wong LJ. Molecular genetics of mitochondrial disorders. Dev Disabil Res Rev. 2010;16(2):154-162. doi:10.1002/ddrr.104
Method Description
Next-generation sequencing (NGS) is used to test for the presence of variants within the mitochondrial genome (includes 13 protein coding genes, 22 transfer RNA genes, and 2 ribosomal RNA genes) and to determine the mitochondrial haplogroup of the patient. Large deletions within the mitochondrial genome are first detected by gel electrophoresis (as size-shifted polymerase chain reaction bands), and the locations of the deletions in the mitochondrial DNA are then determined from the NGS data. Droplet digital polymerase chain reaction (ddPCR) is utilized to confirm the presence of large deletions and determine heteroplasmy level.(Unpublished Mayo method)
The haplogroup is computed using the software package HaploGrep and PhyloTree.(Weissensteiner H, Pacher D, Kloss-Brandstatter A, et al. HaploGrep 2: mitochondrial haplogroup classification in the era of high-throughput sequencing. Nucleic Acids Res. 2016;44[W1]:W58-W63. doi:10.1093/nar/gkw233; van Oven M, Kayser M. Updated comprehensive phylogenetic tree of global human mitochondrial DNA variation. Hum Mutat. 2009;30[2]:E386-E394. doi:10.1002/humu.20921. Available at www.phylotree.org)
Day(s) Performed
Varies
Report Available
28 to 42 daysSpecimen Retention Time
Whole blood: 28 days (if available); Saliva: 30 days (if available); Extracted DNA: 3 months; Blood spots: 1 year (if available)Performing Laboratory
Mayo Clinic Laboratories in Rochester
Test Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
81460-Whole Mitochondrial Genome
81465-Whole Mitochondrial Genome Large Deletion Analysis
88233-Tissue culture, skin, solid tissue biopsy (if appropriate)
88240-Cryopreservation (if appropriate)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| MITOP | Mitochondrial Full Genome Analysis | 101152-7 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 55281 | Result Summary | 50397-9 |
| 55282 | Result | 82939-0 |
| 55283 | Interpretation | 69047-9 |
| 55284 | Additional Information | 48767-8 |
| 55285 | Specimen | 31208-2 |
| 55286 | Source | 31208-2 |
| 55287 | Released By | 18771-6 |