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Test Code WESPM Whole Exome Sequencing plus Whole Mitochondrial Genome Sequencing, Varies

Advisory Information

This test is only available for trios (proband, biological mother, and biological father). This test cannot be performed unless whole blood samples are submitted from the patient and both biological parents.

Additional Testing Requirements

Samples from both biological parents and the patient are required. Each parental specimen must have a separate order for WES / Whole Exome Sequencing, Varies.

Necessary Information

1. Complete the Patient Information and Informed Consent forms within the Whole Exome Sequencing: Ordering Checklist, Patient Information, and Informed Consent forms, available in Special Instructions.

2. In addition, submit relevant clinic notes and a pedigree. Send all paperwork with the specimens to the laboratory. The paperwork may also be faxed directly to 507-284-1759.

Specimen Required

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.

Specimen Type: Whole blood


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 specimen in original tube.

3. Label the parental samples with full name and date of birth. Do not label the parental samples with the child's name.

Additional Information: To ensure minimum volume and concentration of DNA is met, the preferred volume of blood must be submitted. Testing may be canceled if DNA requirements are not met.

Specimen Stability Information: Ambient (preferred)/Refrigerated


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 in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Whole Exome Sequencing: Ordering Checklist, Patient Information, and Informed Consent in Special Instructions.

Secondary ID


Useful For

Establishing a molecular diagnosis in patients with a known or suspected genetic disorder


Establishing a diagnosis of mitochondrial disease that results from variants in the mitochondrial genome


Second-tier testing for patients in whom previous genetic testing for specific syndromes or specific mitochondrial disease-related genes was negative


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


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

Profile Information

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

Testing Algorithm

1. Order this test for the patient (proband).

2. Order WES / Whole Exome Sequencing, Varies for the patient's biological parents. Parental samples will not receive mitochondrial full-genome testing.

3. The cost of analysis for parental samples is applied to the patient’s test. Family members will not be charged separately.

4. Complete the Whole Exome Sequencing: Ordering Checklist, Patient Information, and Informed Consent forms (see Special Instructions) and send to the laboratory along with the specimen.


In addition to analysis of variants associated with the patient's reported phenotype, analysis for reportable secondary findings in genes included in the American College of Medical Genetics and Genomics (ACMG) recommendations will be included.(1) Individuals may opt-out of receiving these test results.


Sanger sequencing or other orthogonal methods may be performed for verification of results.


See Whole Exome Sequencing (WES): Questions and Answers for Providers in Special Instructions for additional information.

Method Name

WES: Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing

MITOP: Long-Range Polymerase Chain Reaction (LRPCR) followed by Next-Generation Sequencing (NGS)

Reporting Name

Whole Exome Sequencing plus mtDNA

Specimen Type


Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Ambient (preferred)

Reject Due To

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

Clinical Information

The results of this testing can help identify a molecular diagnosis in patients with a known or suspected genetic disorder, 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

-Reproductive decision-making


Whole Exome Sequencing:

Many patients with suspected genetic disorders remain without a diagnosis despite having a phenotype that is suggestive of an underlying genetic etiology, such as developmental delay and dysmorphic features. These diagnostic odyssey patients have often had numerous negative or inconclusive genetic tests previously, including karyotype, chromosomal microarray, and various single or multigene assays. Identification of a specific diagnosis can assist in understanding the natural history of a condition, targeting medical management, and providing information to family members about the inheritance pattern and recurrence risks of the condition.


This test uses next-generation sequencing (NGS) technology to assess for variants within the coding regions (exons) of approximately 23,000 genes simultaneously. The patient's biological parents must be available and able to provide a blood sample, which is used for comparison purposes. Based upon published reports, a diagnosis is identified in trio-based whole exome sequencing in approximately 25% to 37% of cases.(2-4)


Indications for whole exome sequencing include but are not limited to(5):

-Patient with a phenotype 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 patient)

-Patient with a phenotype 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)

-Patient 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)

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


See Whole Exome Sequencing (WES): Questions and Answers for Providers in Special Instructions for additional information.


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 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 (mtDNA). This includes certain types of myopathies and neuro-ophthalmologic diseases, such as mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes (MELAS), myoclonic epilepsy with ragged red fibers (MERRF), mitochondrial myopathy (MM), neurogenic muscle weakness, ataxia, retinitis pigmentosa (NARP), Leigh syndrome, Leber hereditary optic neuropathy (LHON), and chronic progressive external ophthalmoplegia (CPEO). 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 variant mitochondria present with more severe disease than those with lower percentages of variant alleles. The sensitivity for the detection of variant alleles in a background of wild-type (or normal) mitochondrial sequences by NGS is approximately 10%.

Reference Values


An interpretive report will be provided that includes variants likely causative of the patient's reported clinical features, variants possibly relevant to the patient's reported clinical features, variants in genes of uncertain significance (GUS), and medically actionable secondary findings (unless the patient opts out).



An interpretive report will be provided.


An interpretive report will be provided.


All detected variants 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 and/or additional data detailing their potential or known significance.


The degree of heteroplasmy of each single nucleotide or insertion and deletion (INDEL) 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 PCR.


Patients who consent to receive medically actionable secondary findings are evaluated for pathogenic and likely pathogenic variants as recommended by ACMG.(1) Variants of uncertain significance (VUS) in these genes are not reported. Parental origin of reportable variants is stated. Variants that are present in a parent but absent from the proband are not evaluated.


The absence of a reportable secondary finding does not guarantee that there are no pathogenic or likely pathogenic variants in these genes, as portions of the genes may not be adequately covered by this testing methodology. If a patient opts-out of receiving these results, these variants will not be reported unless they occur in a gene that is clinically related to the patient's presenting phenotype.

Clinical Reference

1. Kalia SS, Adelman K, Bale SJ, et al: Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. Genet Med 2017;19(2):249-255

2. Yang Y, Muzny DM, Xia F, et al: Molecular findings among patients referred for clinical whole-exome sequencing. JAMA 2014;312(18):1870-1879

3. Lee H, Deignan JL, Dorrani N, et al: Clinical exome sequencing for genetic identification of rare Mendelian disorders. JAMA 2014;312(18):1880-1887

4. 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;17:578-586

5. ACMG Board of Directors: Points to consider in the clinical application of genomic sequencing. Genet Med 2012;14(8):759-761

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;17(5):405-424

7. Iglesias A, Anyane-Yeboa K, Wynn J, et al: The usefulness of whole-exome sequencing in routine clinical practice. Genet Med 2014;16:922-931

8. ACMG Board of Directors: ACMG policy statement: points to consider for informed consent for genome/exome sequencing. Genet Med 2015;15(9):748-749

9. Munnich A, Rotig A, Cormier-Daire V, Rustin P: Chapter 99: Clinical presentation of respiratory chain deficiency. In The Metabolic and Molecular Bases of Inherited Disease. Edited by D Valle, AL Beaudet, B Vogelstein, et al. McGraw-Hill Medical. Retrieved 2013. Available at

10. Wallace DC, Lott MT, Brown MD, Kerstann K: Chapter 105: Mitochondria and neuro-ophthalmologic diseases. In The Metabolic and Molecular Bases of Inherited Disease. Edited by D Valle, AL Beaudet, B Vogelstein, et al. McGraw-Hill Medical. Retrieved 2013.

11. Wong LJ: Molecular genetics of mitochondrial disorders. Dev Disabil Res Rev 2010 Jun;16(2):154-162

Day(s) and Time(s) Performed

Whole Exome Sequencing: Performed weekly, Varies

Mitochondrial Full Genome Analysis: Monday through Friday; Varies

Analytic Time

Whole Exome Sequencing: 12 weeks/Mitochondrial Full Genome Analysis: 8 weeks

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. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information


81416 x 2



81479 (if appropriate for government payers)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
WESPM Whole Exome Sequencing plus mtDNA In Process


Result ID Test Result Name Result LOINC Value
55281 Result Summary 50397-9
113160 Interpretation 69047-9
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