Nuclear Mitochondrial Gene Panel - Clinical Genetic Test - GTR

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Nuclear Mitochondrial Gene Panel

Clinical Genetic Test

offered by

Mayo Clinic Laboratories

View lab's test page

GTR Test Accession: GTR000604274.2

MITOCHONDRIAL DISEASE

Last updated in GTR: 2023-06-06

Last annual review date for the lab: 2023-05-30 Past due

At a Glance

Test purpose:

Diagnosis

Conditions (1):

Mitochondrial disease

Genes (221):

AARS2 (6p21.1); ABAT (16p13.2); ABCB7 (Xq13.3); ACACA (17q12); ACAD9 (3q21.3) more...

Methods (2):

Molecular Genetics - Deletion/duplication analysis: Next-Generation (NGS)/Massively parallel sequencing (MPS); ...

Target population:

Individuals with clinical features of nuclear mitochondrial disease.

Clinical validity:

Not provided

Clinical utility:

Not provided

Ordering Information

Offered by:

Mayo Clinic Laboratories
View lab's website
View lab's test page

Test short name:

NMITO

Specimen Source:

Peripheral (whole) blood
View specimen requirements

Who can order:

Genetic Counselor
Health Care Provider
Licensed Dentist
Licensed Physician
Nurse Practitioner
Physician Assistant
Public Health Mandate
Registered Nurse

Test Order Code:

NMITO
View other test codes

LOINC codes:

**LOINC codes notice

Lab contact:

Elizabeth Selner, MS, CGC, Certified Genetic counselor, CGC, Genetic Counselor
gcmolgen@mayo.edu
800-533-1710

Contact Policy:

Laboratory can only accept contact from health care providers. Patients/families are encouraged to discuss genetic testing options with their health care provider.

How to Order:

https://www.mayocliniclabs.com/test-catalog/Overview/617090#Specimen
Order URL

Test service:

Clinical Testing/Confirmation of Mutations Identified Previously
Comment: FMTT
OrderCode: FMTT

Test development:

Test developed by laboratory (no manufacturer test name)

Informed consent required:

Based on applicable state law

Pre-test genetic counseling required:

Post-test genetic counseling required:

Recommended fields not provided:

Test strategy

Conditions

Total conditions: 1

Condition/Phenotype	Identifier

Test Targets

Genes

Total genes: 221

Gene	Associated Condition	Germline or Somatic	Allele (Lab-provided)	Variant in NCBI

Methodology

Total methods: 2

Method Category

Test method

Instrument

Deletion/duplication analysis

Next-Generation (NGS)/Massively parallel sequencing (MPS)

Mutation scanning of the entire coding region

Next-Generation (NGS)/Massively parallel sequencing (MPS)

Illumina NovaSeq6000

Clinical Information

Test purpose:

Diagnosis

Target population:

Individuals with clinical features of nuclear mitochondrial disease.

View citations (1)

Barca E, Long Y, Cooley V, Schoenaker R, Emmanuele V, DiMauro S, Cohen BH, Karaa A, Vladutiu GD, Haas R, Van Hove JLK, Scaglia F, Parikh S, Bedoyan JK, DeBrosse SD, Gavrilova RH, Saneto RP, Enns GM, Stacpoole PW, Ganesh J, Larson A, Zolkipli-Cunningham Z, Falk MJ, Goldstein AC, Tarnopolsky M, Gropman A, Camp K, Krotoski D, Engelstad K, Rosales XQ, Kriger J, Grier J, Buchsbaum R, Thompson JLP, Hirano M. Mitochondrial diseases in North America: An analysis of the NAMDC Registry. Neurol Genet. 2020;6(2):e402. doi:10.1212/NXG.0000000000000402. Epub 2020 Mar 02. PMID: 32337332.

Variant Interpretation:

What is the protocol for interpreting a variation as a VUS?
All detected variants are evaluated according to the most recent American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP) recommendations. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Are family members with defined clinical status recruited to assess significance of VUS without charge?
Yes. Contact lab for details

Will the lab re-contact the ordering physician if variant interpretation changes?
No. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time.

Research:

Is research allowed on the sample after clinical testing is complete?
Research testing is only performed under IRB approved protocol with an opt-out policy in place.

Recommended fields not provided:

Clinical validity, Clinical utility, Sample negative report, Sample positive report

Technical Information

Test Procedure:

Next-generation sequencing and/or Sanger sequencing is performed to test for the presence of variants in coding regions and intron/exon boundaries of the genes analyzed, as well as some other regions that have known disease-causing variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% … View more

Test Confirmation:

Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria. PCR-based methods and/or Sanger sequencing is used to confirm variants detected by NGS when appropriate

Availability:

Tests performed
Entire test performed in-house

Analytical Validity:

At least 99% of the bases are covered at a read depth >30X. Sensitivity is estimated at >99% for single nucleotide variants, >94% for indels up to 39 base pairs, >95% for deletions up to 75 base pairs and insertions up to 47 base pairs.

Assay limitations:

Clinical Correlations: Test results should be interpreted in context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete. If testing was performed because of a clinically significant family history, it is often useful to first test an … Clinical Correlations: Test results should be interpreted in context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete. If testing was performed because of a clinically significant family history, it is often useful to first test an affected family member. Detection of a reportable variant in an affected family member would allow for more informative testing of at risk individuals. To discuss the availability of additional testing options, for assistance in general test selection, or for assistance in the interpretation of these results, Mayo Clinic Laboratory genetic counselors can be contacted at 800-533-1710. Technical Limitations: Next-generation sequencing may not detect all types of genomic variants. In rare cases, false-negative or false-positive results may occur. The depth of coverage may be variable for some target regions, but assay performance below the minimum acceptable criteria or for failed regions will be noted. Given these limitations, negative results do not rule out the diagnosis of a genetic disorder. If specific clinical disorders are suspected, evaluation by alternative methods can be considered. If the patient has had an allogeneic hematopoietic stem cell transplant or a recent heterologous blood transfusion, these results may be inaccurate due to the presence of donor DNA. Call Mayo Clinic Laboratories for instructions for testing patients who have received a bone marrow transplant. There may be regions of genes that cannot be effectively amplified for sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. Confirmation of select reportable variants will be performed by alternate methodologies based on internal laboratory criteria. This assay will not reliably detect insertions/deletions (indels) of 40 or more base pairs (bp), including Alu insertions, long interspersed nuclear elements (LINES), and short interspersed nuclear elements (SINES). The bioinformatics software pipeline is verified to detect 95% of deletions up to 75 bp and insertions up to 47 bp. Additionally, low level mosaic variants may not be detected. This test is not designed to differentiate between somatic and germline variants. If there is a possibility that any detected variant is somatic, additional testing may be necessary to clarify the significance of results. Reclassification of Variants-Policy: At this time, it is not standard practice for the laboratory to systematically review previously classified variants on a regular basis. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time. Variant Evaluation: Evaluation and categorization of variants is performed using published American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP)recommendations as a guideline.(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. Variants classified as benign or likely benign are not reported. Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and periodic updates to these tools may cause predictions to change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgment. Intronic and synonymous sequence variants not predicted to impact splicing or otherwise contribute to disease are not reported. View more

Proficiency testing (PT):

Is proficiency testing performed for this test?
Yes

Method used for proficiency testing:
Platform PT performed

VUS:

Software used to interpret novel variations
Variants may be analyzed using any combination of the following: Alamut, REVEL, Polyphen-2, SIFT, AGVGD, MutationTaster, SpliceSiteFinder-like, MaxEntScan, NNSPLICE, GeneSplicer, gene-specific online databases, ISCA, UCSC Genome Browser

Laboratory's policy on reporting novel variations
All novel alterations and copy number variants are evaluated for potential pathogenicity and included in the written report, accordingly.

Recommended fields not provided:

Citations to support assay limitations, Description of internal test validation method, Citations for Analytical validity, PT Provider, Description of PT method, Major CAP category, CAP category, CAP test list

Regulatory Approval

FDA Review:

Category: FDA exercises enforcement discretion

Additional Information

Reviews:

Genereviews

PubMed Clinical Queries

Clinical resources:

Molecular resources:

View MT-TC variations in ClinVar

View MT-ND1 variations in ClinVar

View MT-ND4 variations in ClinVar

View MT-ND5 variations in ClinVar

View MT-ND6 variations in ClinVar

View MT-TA variations in ClinVar

View MT-TD variations in ClinVar

View MT-TF variations in ClinVar

View MT-TH variations in ClinVar

View MT-TK variations in ClinVar

View MT-TL1 variations in ClinVar

View MT-TL2 variations in ClinVar

View MT-TM variations in ClinVar

View MT-TQ variations in ClinVar

View MT-TR variations in ClinVar

View MT-TS1 variations in ClinVar

View MT-TS2 variations in ClinVar

View MT-TT variations in ClinVar

View MT-TV variations in ClinVar

View MT-TW variations in ClinVar

View MT-TY variations in ClinVar

Consumer resources:

Genetic Alliance

MedlinePlus

IMPORTANT NOTE: NIH does not independently verify information submitted to GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.