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HelpTest Code WESMT Whole Exome and Mitochondrial Genome Sequencing, 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 NMITO / Nuclear Mitochondrial Gene Panel, Next-Generation Sequencing (NGS), 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.
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 Variant, 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 and Genome Sequencing Information and Test Ordering Guide.
Shipping Instructions
Necessary Information
Whole Exome Sequencing: Ordering Checklist is required. Fill out one form for the family and send with the specimens.
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.
3. Whole blood collected postnatal from an umbilical cord is also acceptable. See Additional Information
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. For postnatal umbilical cord whole blood specimens, maternal cell contamination studies are recommended to ensure test results reflect that of the patient tested. A maternal blood specimen is required to complete maternal cell contamination studies. Order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on both the cord blood and maternal blood specimens under separate order numbers.
Specimen Type: Saliva
Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.
Supplies:
DNA Saliva Kit High Yield (T1007)
Saliva Swab Collection Kit (T786)
Container/Tube:
Preferred: High-yield DNA saliva kit
Acceptable: Saliva swab
Specimen Volume: 1 Tube if using T1007 or 2 swabs if using T786
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: 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.
Send: Ambient (preferred)/Refrigerated
Additional Information:
1. Blood spot specimens are acceptable but not recommended. Due to lower quantity/quality of DNA yielded from blood spots, 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.
2. Due to lower concentration of DNA yielded from blood spot, it is possible that 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: 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/or 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 or tissue
Container/Tube: T-25 flask
Specimen Volume: 2 Flasks
Collection Instructions: Submit confluent cultured fibroblast cells from a 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/or 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: 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: Extracted DNA
Container/Tube:
Preferred: Screw Cap Micro Tube, 2mL with skirted conical base
Acceptable: Matrix tube, 1mL
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
This does not include cultured chorionic villi.
Container/Tube: T-25 flask
Specimen Volume: 2 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.
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 are 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.
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.
3. If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:
Useful For
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
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
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| WESDX | Whole Exome Sequencing | Yes | Yes |
| MITOP | Mitochondrial Full Genome Analysis | Yes | Yes |
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| MATCC | Maternal Cell Contamination, B | Yes | No |
| G226 | Number of Comparators for WESDX | No, (Bill Only) | No |
| CULFB | Fibroblast Culture for Genetic Test | Yes | No |
| CULAF | Amniotic Fluid Culture/Genetic Test | Yes | No |
Testing Algorithm
This test is a single order that performs whole exome sequencing and mitochondrial full genome analysis concurrently, with independently reported results. When this test is resulted, the component tests, WESDX and MITOP, are billed separately.
Prenatal specimens:
If an amniotic fluid specimen or cultured amniocytes are received, an amniotic fluid culture will be performed at an additional charge.
If a chorionic villi specimen or cultured chorionic villi are 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.
Skin biopsy or cultured fibroblast specimens:
For skin biopsy or cultured fibroblast specimens, a fibroblast culture will be performed at an additional charge. If viable cells are not obtained, the client will be notified.
Cord blood:
For cord blood specimens that have an accompanying maternal blood specimen, maternal cell contamination studies will be performed at an additional charge.
Special Instructions
Method Name
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) and Droplet Digital Polymerase Chain Reaction (ddPCR) as needed
Reporting Name
Exome and Mitochondrial GenomeSpecimen Type
VariesSpecimen Stability Information
| Specimen Type | Temperature | Time |
|---|---|---|
| Varies | Varies | |
Reject Due To
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.Clinical Information
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 whole exome sequencing (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
An interpretive report will be provided.
Day(s) Performed
Varies
Report Available
84 daysSpecimen Retention Time
Whole blood: 25 days (if available); Extracted DNA: 3 months, Saliva: 30 days; 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
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)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| WESMT | Exome and Mitochondrial Genome | 86205-2 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 55281 | Result Summary | 50397-9 |
| 616410 | Interpretation | 69047-9 |
| 616411 | Specimen | 31208-2 |
| 55282 | Result | 82939-0 |
| 55283 | Interpretation | 69047-9 |
| 616412 | Source | 31208-2 |
| 616413 | Released By | 18771-6 |
| 55284 | Additional Information | 48767-8 |
| 55285 | Specimen | 31208-2 |
| 55286 | Source | 31208-2 |
| 55287 | Released By | 18771-6 |