Test Catalog

Test Id : WESMT

Whole Exome and Mitochondrial Genome Sequencing, Varies

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

Serving as a first-tier test to identify a molecular and/or mitochondrial diagnosis in patients with suspected genetic disorders, which can allow for:

-Better understanding of the natural history/prognosis

-Targeted management (anticipatory guidance, management changes, specific therapies)

-Predictive testing of at-risk family members

-Testing and exclusion of disease in siblings or other relatives

-Recurrence risk assessment

 

Serving as a second-tier test for patients in whom previous genetic testing was negative.

 

Providing a potentially cost-effective alternative to establishing a molecular diagnosis compared to performing multiple independent molecular assays.

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

This test provides results from both whole exome sequencing and mitochondrial genome sequencing.

 

Whole exome sequencing utilizes next-generation sequencing (NGS) to detect single nucleotide and copy number variants within the protein-coding regions of approximately 20,000 genes. See Method Description for additional details.

 

Mitochondrial genome sequencing includes amplification of the entire mitochondrial genome by long-range polymerase chain reaction followed by sequencing on the NGS platform to evaluate for variants within the mitochondrial genome.

 

Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, recurrence risk assessment, familial screening, and genetic counseling.

 

It is highly recommended that samples are submitted from the patient (proband), the patient's biological mother, and the patient's biological father (trio analysis). However, testing for singletons (patient only), duos (patient and one relative to be used as a comparator), and nontraditional trios (patient and 2 relatives to be used as comparators) will also be accepted if the patient’s biological mother and biological father are not available for testing.

 

Additional first-tier testing may be considered/recommended. For more information, see the Ordering Guidance section.

Profile Information
A profile is a group of laboratory tests that are ordered and performed together under a single Mayo Test ID. Profile information lists the test performed, inclusive of the test fee, when a profile is ordered and includes reporting names and individual availability.

Test Id Reporting Name Available Separately Always Performed
WESDX Whole Exome Sequencing Yes Yes
MITOP Mitochondrial Full Genome Analysis Yes Yes

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

If a cord blood specimen is received, maternal cell contamination testing will be added and performed at an additional charge.

 

If skin biopsy is received, fibroblast culture and cryopreservation for biochemical studies will be added and performed at an additional charge.

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

WESDX: Sequence Capture and Targeted Next-Generation Sequencing followed by Sanger Sequencing or Quantitative Polymerase Chain Reaction (qPCR)

MITOP: 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

Exome and Mitochondrial Genome

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

Exome

Exome Sequencing

Exon

Exons

WES

Whole

Whole exome

Whole-exome

Singleton

Duo

Trio

Quad

Non-traditional trio

Genome

Genomic

WESDX

WESMT

Chronic progressive external ophthalmoplegia

CPEO

Kearns-Sayre syndrome

Leber's hereditary optic neuropathy

Leigh syndrome

LHON

MELAS

MERRF

mtDNA

Myoclonic Epilepsy with Ragged Red Fibers

NARP

Neurogenic Muscle Weakness, Ataxia, and Retinitis Pigmentosa

Next Gen Sequencing Test

Pearson syndrome

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

If a cord blood specimen is received, maternal cell contamination testing will be added and performed at an additional charge.

 

If skin biopsy is received, fibroblast culture and cryopreservation for biochemical studies will be added and performed at an additional charge.

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

The American College of Medical Genetics and Genomics (ACMG) recommends that whole exome sequencing be considered as a first-tier or second-tier test for patients with one or more congenital anomalies, or developmental delay or intellectual disability with onset prior to age 18 years.(1)

 

If a specific diagnosis is suspected, single gene testing or panel testing may be a more appropriate first-tier testing option.

 

This test is for affected patients (probands) only. For family member specimens being sent as comparators, order CMPRE / Family Member Comparator Specimen for Exome Sequencing, Varies. If this test is ordered on a family member comparator specimen, the test will be canceled and CMPRE will be performed as the appropriate test.

 

This test cannot support detection of deep intronic variants or trinucleotide repeat variants; variants in the mitochondrial genome are detected.

-For whole exome sequencing only, order WESDX / Whole Exome Sequencing for Hereditary Disorders, Varies.

-If mitochondrial genome testing only is needed, order MITOP / Mitochondrial Full Genome Analysis, Next-Generation Sequencing (NGS), Varies.

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

 

This test is not appropriate for identification of somatic variants in solid tumors. If this testing is needed, order MCSTP / MayoComplete Solid Tumor Panel, Next-Generation Sequencing, Tumor.

 

This testing does not provide genotyping of patients for pharmacogenomic purposes. For an assessment for genes with strong drug-gene associations, order PGXQP / Focused Pharmacogenomics Panel, Varies.

 

Targeted testing for familial variants (also called site-specific or known variant testing) is available for variants identified by this test. See FMTT / Familial Mutation, Targeted Testing, Varies.

Additional Testing Requirements

To order testing with comparator specimens, see the following steps:

1. Order this test on the patient (proband)

2. Order CMPRE / Family Member Comparator Specimen for Exome Sequencing, Varies on all family members being submitted as comparator specimens.

a. When available, the patient’s biological mother and biological father are the preferred family member comparators.

b. If one or both of the patient’s biological parents are not available for testing, specimens from other first-degree relatives (siblings or children) can be used as comparators. Contact the laboratory at 800-533-1710 for approval to send specimens from other relatives.

c. The cost of analysis for family member comparator specimens is applied to the patient’s (proband’s) test. Family members will not be charged separately.

3. Collect patient (proband) and family member specimens. Label specimens with full name and birthdate. Do not label family members’ specimens with the proband’s name.

4. Complete the signature sections of the Informed Consent (required for New York State clients) portion of Whole Exome Sequencing: Ordering Checklist.

5. If the patient wishes to opt-out of receiving secondary findings or change the DNA storage selection, select the appropriate boxes in the Informed Consent section.

6. Attach clinic notes from specialists relevant to patient’s clinical features, if available.

7. Attach pedigree information, if available.

8. Send paperwork to the laboratory along with the specimens. If not sent with the specimen, fax a copy of the paperwork to 507-284-1759, Attention: WES Genetic Counselors.

 

For more information see Whole Exome Sequencing (WES): Questions and Answers for Providers.

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

Necessary Information

Whole Exome Sequencing: Ordering Checklist is required. Fill out one form for the family and send with the specimens.

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: 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 specimen in original tube.

Specimen Stability Information: Ambient (preferred)/Refrigerated

Additional Information: If a cord blood specimen is received, MATCC / Maternal Cell Contamination, Molecular Analysis, Varies will be performed at an additional charge.

 

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 FIBR / Fibroblast Culture for Biochemical and Molecular Testing, Tissue. An additional 4 weeks is required to culture fibroblasts before genetic testing can occur.

 

Specimen Type: Cultured fibroblasts

Container/Tube: T-25 flask

Specimen Volume: 2 flasks

Collection Instructions: Submit confluent cultured fibroblast cells from a skin biopsy from another laboratory. Cultured cells from a prenatal specimen will not be accepted.

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

Additional Information: A separate culture charge will be assessed under FIBR / Fibroblast Culture for Biochemical and Molecular Testing, Tissue. An additional 4 weeks is required to culture fibroblasts before genetic testing can occur.

 

Specimen Type: Blood spot

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

Container/Tube:

Preferred: Collection card (Whatman Protein Saver 903 Paper)

Acceptable: PerkinElmer 226 (formerly Ahlstrom 226) filter paper, or blood spot collection card

Specimen Volume: 5 Blood spots

Collection Instructions:

1. An alternative blood collection option for a patient older than 1 year of age is finger stick. For infants younger than 1 year, a heel stick should be used. 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. For collection instructions, see Blood Spot Collection Instructions.

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

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

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

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

Forms

1. Whole Exome Sequencing: Ordering Checklist is required.

2. New York Clients-Informed consent is required, included in the above form. Document on the request form or electronic order that a copy is on file.

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

All specimens will be evaluated 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 Ambient (preferred)
Frozen
Refrigerated

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

Serving as a first-tier test to identify a molecular and/or mitochondrial diagnosis in patients with suspected genetic disorders, which can allow for:

-Better understanding of the natural history/prognosis

-Targeted management (anticipatory guidance, management changes, specific therapies)

-Predictive testing of at-risk family members

-Testing and exclusion of disease in siblings or other relatives

-Recurrence risk assessment

 

Serving as a second-tier test for patients in whom previous genetic testing was negative.

 

Providing a potentially cost-effective alternative to establishing a molecular diagnosis compared to performing multiple independent molecular assays.

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

This test provides results from both whole exome sequencing and mitochondrial genome sequencing.

 

Whole exome sequencing utilizes next-generation sequencing (NGS) to detect single nucleotide and copy number variants within the protein-coding regions of approximately 20,000 genes. See Method Description for additional details.

 

Mitochondrial genome sequencing includes amplification of the entire mitochondrial genome by long-range polymerase chain reaction followed by sequencing on the NGS platform to evaluate for variants within the mitochondrial genome.

 

Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, recurrence risk assessment, familial screening, and genetic counseling.

 

It is highly recommended that samples are submitted from the patient (proband), the patient's biological mother, and the patient's biological father (trio analysis). However, testing for singletons (patient only), duos (patient and one relative to be used as a comparator), and nontraditional trios (patient and 2 relatives to be used as comparators) will also be accepted if the patient’s biological mother and biological father are not available for testing.

 

Additional first-tier testing may be considered/recommended. For more information, see the Ordering Guidance section.

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

If a cord blood specimen is received, maternal cell contamination testing will be added and performed at an additional charge.

 

If skin biopsy is received, fibroblast culture and cryopreservation for biochemical studies will be added and performed at an additional charge.

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

Whole Exome Sequencing:

This test uses next-generation sequencing technology to assess patients with suspected underlying genetic disorders for single nucleotide and copy number variants within the protein-coding regions (exons and splice junctions) of approximately 20,000 genes simultaneously. Indications for whole exome sequencing include but are not limited to(1,2):

-Patients with one or more congenital anomalies

-Patients with developmental delay or intellectual disability with onset prior to age 18 years

-Patients with a phenotype and/or family history that strongly suggests an underlying genetic cause, yet genetic tests for that phenotype have failed to arrive at a diagnosis (diagnostic odyssey)

-Patients with a phenotype and/or family history that strongly suggests an underlying genetic cause, but the phenotype does not fit with one specific disorder (numerous individual genetic tests would be required for evaluation)

-Patients with a suspected genetic disorder that has numerous underlying genetic causes, making analysis of numerous genes simultaneously a more practical approach than single-gene testing (condition is genetically heterogeneous)

-Patients with a suspected genetic disorder for which specific molecular genetic testing is not yet available

-Patients with an atypical presentation of a genetic disorder

 

It is highly recommended that samples are also submitted from the patient’s biological mother and biological father, which are used for comparison purposes (trio analysis). Based upon published reports, a diagnosis is identified in trio-based WES in approximately 25% to 37% of cases, with slightly lower diagnostic yield in non-trio WES.(3,4,5) However, testing for singletons (patient only), duos (patient and one family member to be used as a comparator), and non-traditional trios (patient and 2 family members to be used as comparators) will also be accepted if both biological parents are unavailable.

 

Mitochondrial Full Genome Analysis:

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

Variants of interest are evaluated according to American College of Medical Genetics and Genomics (ACMG) recommendations.(6) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance. Separate test reports will be issued for WESDX / Whole Exome Sequencing for Hereditary Disorders, Varies and MITOP / Mitochondrial Full Genome Analysis, Next-Generation Sequencing (NGS), Varies.

 

For whole exome sequencing, variants are reported in one of the following categories:

-Likely Causative: variants with a high degree of suspicion for causing the patient’s reported clinical features

-Possibly Relevant: variants that may be related to the patient’s clinical features or variants in genes of uncertain significance (GUS)

-Secondary Findings: Medically actionable variants unrelated to the indication for testing (see below for additional information).

 

For mitochondrial variants, 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.

 

It is possible that a variant may not be recognized as the underlying cause of disease due to incomplete scientific knowledge about the function of all genes in the human genome and/or the impact of variants in those genes.

 

Secondary Findings:

Patients are evaluated for medically actionable secondary findings and these findings are reported in accordance with the ACMG recommendations.(7) Variants in these genes will not be evaluated or reported if the patient selects to opt out of this evaluation, unless they overlap with the patient’s reported clinical phenotype.

 

The presence of a variant in family member comparator samples is stated on the patient's (proband's) report unless family members opt out of secondary findings. If the patient (proband) opts out, secondary findings will not be reported for any family member. Variants that are present in family member comparators but absent from the patient (proband) are not evaluated.

 

The absence of a reportable secondary finding does not guarantee that there are no disease-associated or likely disease-associated variants in these genes, as portions of the genes may not be adequately covered by this testing methodology.

 

Exome Reanalysis:

Healthcare providers may contact the laboratory at 800-533-1710 to request reanalysis of the patient’s exome due to new patient clinical features, advances in genetic knowledge, or changes in testing methodology. A charge may apply for reanalysis.

 

Raw Data Requests:

Requests for the raw data obtained from whole exome sequencing should be directed to the laboratory. A separate fee may apply. Raw data will be released for individuals who complete a Mayo Clinic release of information form. If raw data for family member comparators is requested, it will only be released with an accompanying request for the proband’s raw data. Contact the laboratory for instructions on completing the release of information form. The laboratory is not responsible for providing software or other tools needed to visualize, filter, or interpret this data.

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

Clinical Correlations:
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.

 

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.

 

To discuss the availability of further testing options, or for assistance in the interpretation of these results, Mayo Clinic Laboratory genetic counselors can be contacted at 1-800-533-1710.

 

Technical Limitations:
If the patient has had an allogeneic hematopoietic stem cell transplant or a recent heterologous blood transfusion, 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.

 

Whole exome 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. Given these limitations, negative results do not rule out the diagnosis of a genetic disorder. If a specific clinical disorder is suspected, evaluation by alternative methods can be considered.

 

There may be regions of genes that cannot be effectively evaluated by 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 test is validated to detect 95% of deletions up to 75 base pairs (bp) and insertions up to 47 bp. Deletions/insertions (delins) of 40 or more bp, including mobile element insertions, may be less reliably detected than smaller delins.

 

Deletion/Duplication Analysis:

This analysis detects multi-exon deletions/duplications; however, in some instances single exon resolution can be achieved. The reliability of detection can be variable due to isolated reduction in sequence coverage or inherent genomic complexity. Balanced structural rearrangements (such as translocations and inversions) may not be detected.

 

This test is not designed to detect low levels of mosaicism or 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:
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 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.

 

Variant Evaluation:
Evaluation and categorization of variants is performed using published American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology recommendations as a guideline.(6) 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 judgement.

 

Rarely, incidental findings or secondary findings outside of the genes recommended by the ACMG may implicate another predisposition or presence of active disease. These findings will be carefully reviewed to determine whether they will be reported.

 

Data Sharing:

Deidentified variant information may be shared in public genetic databases, such ClinVar and Matchmaker Exchange.

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

1. Manickam K, McClain MR, Demmer LA, et al: Exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability: an evidence-based clinical guideline of the American College of Medical Genetics and Genomes (ACMG). Genet Med. 2021 Nov;23(11):2029-2037. doi: 10.1038/s41436-021-01242-6

2. ACMG Board of Directors: Points to consider for informed consent for genome/exome sequencing. Genet Med. 2013 Sep;15(9):748-749. doi: 10.1038/gim.2013.94

3. Yang Y, Muzny DM, Xia F, et al: Molecular findings among patients referred for clinical whole-exome sequencing. JAMA. 2014 Nov 12;312(18):1870-1879. doi: 10.1001/jama.2014.14601

4. Lee H, Deignan JL, Dorrani N, et al: Clinical exome sequencing for genetic identification of rare Mendelian disorders. JAMA. 2014 Nov 12;312(18):1880-1887. doi: 10.1001/jama.2014.14604

5. Farwell KD, Shahmirzadi L, El-Khechen D, et al: Enhanced utility of family-centered diagnostic exome sequencing with inheritance model-based analysis: results from 500 unselected families with undiagnosed genetic conditions. Genet Med. 2015 Jul;17(7):578-586. doi: 10.1038/gim.2014.154

6. 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):405-24. doi: 10.1038/gim.2015.30

7. Miller DT, Lee K, Gordon AS, et al: Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2021 update: a policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021Aug;23(8):1391-1398. doi: 10.1038/s41436-021-01171-4

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

Mitochondrial Genome Sequencing:

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)

 

Whole Exome Sequencing:

NGS is performed on DNA extracted from the patient and all submitted comparator samples to test for the presence of variants in coding regions and intron/exon boundaries. The human genome reference GRCh37/hg19 build is used for sequence read alignment. Variants are called using an optimized bioinformatics package. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for deletion-insertions (delins) less than 40 base pairs (bp), above 95% for deletions up to 75 bp, and insertions up to 47 bp. This assay also detects most copy number variants (deletions/duplications) involving 3 or more exons. In some instances, copy number variants less than 3 exons may be detected; however, the reliability of this detection is variable due to isolated reduction in sequence coverage or inherent genomic complexity. Resulting variants are filtered and annotated using public and proprietary resources and presented for analysis and interpretation using a vended interpretation tool. Confirmation of select reportable variants in the proband and submitted comparator samples may be performed by alternate methodologies based on internal laboratory criteria.

 

There may be regions of genes that cannot be effectively evaluated by 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.(Unpublished Mayo method)

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

Supplemental

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.

Varies

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.

12 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; Blood spots, cultured fibroblasts, skin biopsy, cord blood: 1 month

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.

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.

81415-Patient only

81415, 81416-Patient and one family member comparator sample (duo) (as appropriate)

81415, 81416 x 2-Patient and two family member comparator samples (trio or non-traditional trio) (as appropriate)

81415, 81416 x 3-Patient and three family member comparator samples (quad) (as appropriate)

81460-Whole Mitochondrial Genome

81465-Whole Mitochondrial Genome Large Deletion Analysis

88233-Tissue culture, skin, solid tissue biopsy (if appropriate)

88240-Cryopreservation (if appropriate)

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