Test Catalog

Test Id : MITOP

Mitochondrial Full Genome Analysis, Next-Generation Sequencing (NGS), Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

Diagnosis of the subset of mitochondrial diseases that results 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

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

Highlights

Next-generation sequencing (NGS) is used to test for the presence of variants, including: 13 protein coding genes, 22 transfer RNA genes, and 2 ribosomal RNA genes, within the mitochondrial genome

 

Large deletions within the mitochondrial genome and their locations are determined from the NGS data.

 

This assay is only useful for detecting mitochondrial genomic variants. Depletion of mitochondrial DNA levels or variants in mitochondrial genes encoded by the nuclear genome is not within the scope of this assay.

Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

Test Id Reporting Name Available Separately Always Performed
CULFB Fibroblast Culture for Genetic Test Yes No

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

For skin biopsy or cultured fibroblast specimens, fibroblast culture testing will be performed at an additional charge. If viable cells are not obtained, the client will be notified.

 

The following algorithms are available:

-Epilepsy: Unexplained Refractory and/or Familial Testing Algorithm

-Neuromuscular Myopathy Testing Algorithm

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Long-Range Polymerase Chain Reaction (LR-PCR) followed by Next-Generation Sequencing (NGS)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Mitochondrial Full Genome Analysis

Aliases
Lists additional common names for a test, as an aid in searching

mtDNA

MELAS

Myoclonic Epilepsy with Ragged Red Fibers

MERRF

Neurogenic Muscle Weakness, Ataxia, and Retinitis Pigmentosa

NARP

Leigh syndrome

LHON

Chronic progressive external ophthalmoplegia

CPEO

Pearson syndrome

Next Gen Sequencing Test

Leber's hereditary optic neuropathy

Kearns-Sayre syndrome

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

For skin biopsy or cultured fibroblast specimens, fibroblast culture testing will be performed at an additional charge. If viable cells are not obtained, the client will be notified.

 

The following algorithms are available:

-Epilepsy: Unexplained Refractory and/or Familial Testing Algorithm

-Neuromuscular Myopathy Testing Algorithm

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

If testing for variants in the mitochondrial genes encoded by the nuclear genome is requested, order MITON / Mitochondrial Nuclear Gene Panel, Next-Generation Sequencing (NGS), Varies

Shipping Instructions

Ambient blood is preferred to arrive within 96 hours of collection.

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 providers are strongly encouraged to complete the form and send it with the specimen.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

 

Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

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 (preferred)/Refrigerated

 

Specimen Type: Cultured fibroblasts

Container/Tube: T-75 or T-25 flask

Specimen Volume: 1 Full T-75 or 2 full T-25 flasks

Specimen Stability Information: Ambient (preferred)/Refrigerated <24 hours

Additional Information: 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.

 

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: Refrigerated (preferred)/Ambient

Additional Information: 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.

 

Specimen Type: Muscle tissue biopsy

Supplies: Muscle Biopsy Kit (T541)

Collection Instructions: Prepare and transport specimen per instructions in Muscle Biopsy Specimen Preparation Sheet.

Specimen Volume: 10-80 mg

Specimen Stability Information: Frozen (preferred)/Ambient/Refrigerated

 

Specimen Type: Snap frozen nerve tissue biopsy

Collection Instructions: Prepare snap frozen tissue biopsy per surgical procedure

Specimen Volume: 0.25-0.5 cm

Specimen Stability Information: Frozen

 

Specimen Type: Blood spot

Supplies: Card-Blood Spot Collection (Filter Paper) (T493)

Preferred: Collection card (Whatman Protein Saver 903 Paper)

Acceptable: PerkinElmer 226 (formerly Ahlstrom 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 of age is a finger stick. See Dried Blood Spot Collection Tutorial for how to collect blood spots via fingerstick

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. Due to lower concentration of DNA yielded from blood spot, it is possible that additional specimen may be required to complete testing.

2. For collection instructions, see Blood Spot Collection Instructions

3. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777)

4. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800)

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Molecular Genetics: Biochemical Disorders Patient Information (T527)

3. If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

Blood: 1 mL

Muscle tissue biopsy: 20 mg

Nerve tissue biopsy: See Specimen Required.

Blood Spots: 5 punches-3 mm diameter

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

All specimens will be evaluated by at Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

Diagnosis of the subset of mitochondrial diseases that results 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

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

For skin biopsy or cultured fibroblast specimens, fibroblast culture testing will be performed at an additional charge. If viable cells are not obtained, the client will be notified.

 

The following algorithms are available:

-Epilepsy: Unexplained Refractory and/or Familial Testing Algorithm

-Neuromuscular Myopathy Testing Algorithm

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

The mitochondrion occupies a unique position in eukaryotic biology. First, it is the site of energy metabolism, without which aerobic metabolism and life as we know it would not be possible. Second, it is the sole subcellular organelle that is 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, involving virtually any organ system, and 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 that are 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
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

All detected alterations are evaluated according to American College of Medical Genetics and Genomics recommendations.(1) 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. Large deletions will be reported as either homoplasmic or heteroplasmic, but the degree of heteroplasmy will not be estimated, due to possible preferential amplification of the smaller deletion product by long-range polymerase chain reaction.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

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 alteration. Additionally, the predictability of these tools for the determination of pathogenicity is currently unvalidated.

 

Unless reported or predicted to cause disease, alterations in protein coding genes that do not result in an amino acid substitution are not reported. The mitochondrial haplogroup classification of the patient will be reported, but the individual nucleotide changes that define the haplogroup will not be reported. These and common alterations identified for this patient are available upon request.

 

Reclassification of Variants-Policy:

At this time, it is not standard practice for the laboratory to systematically review likely deleterious alterations or variants of uncertain significance that are detected and reported. The laboratory encourages healthcare providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-424

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 September 28, 2020. Available at https://ommbid.mhmedical.com/content.aspx?bookid=2709&sectionid=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 et al, eds. The Online Metabolic and Molecular Basis of Inherited Disease. McGraw-Hill; 2019. Accessed September 28, 2020. Available at https://ommbid.mhmedical.com/content.aspx?bookid=2709&sectionid=225088522

4. Wong LJ: Molecular genetics of mitochondrial disorders. Dev Disabil Res Rev. 2010 Jun;16(2):154-162. doi: 10.1002/ddrr.104

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

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.

 

The haplogroup is computed using the software package HaploGrep.(Kloss-Brandstatter A, Pacher D, Schonherr S, et al: HaploGrep: a fast and reliable algorithm for automatic classification of mitochondrial DNA haplogroups. Hum Mutat. 2011 Jan;32(1):25-32) and PhyloTree.(van Oven M, Kayser M: Updated comprehensive phylogenetic tree of global human mitochondrial DNA variation. Hum Mutat.. 2009;30[2]:E386-E394 Available at www.phylotree.org)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

8 to 10 weeks

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole Blood: 2 weeks (if available); Extracted DNA: 3 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

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® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
MITOP Mitochondrial Full Genome Analysis In Process
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
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

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports