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HelpTest ID WESDX Whole Exome Sequencing for Hereditary Disorders, Varies
Ordering Guidance
The American College of Medical Genetics and Genomics 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 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, this test will be canceled and CMPRE performed as the appropriate test.
This test cannot support detection of deep intronic variants, trinucleotide repeat variants, or variants in the mitochondrial genome.
-For whole exome sequencing plus analysis of the mitochondrial genome, order WESMT / Whole Exome and Mitochondrial Genome Sequencing, Varies.
-If separate mitochondrial genome testing is needed, order MITOP / Mitochondrial Full Genome Analysis, 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 Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.
Prenatal specimens (amniocentesis or chorionic villi) are not currently accepted for this test.
Additional Testing Requirements
To order whole exome testing for the patient and the family member 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' specimens being submitted as comparators.
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, 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, Attn: WES Genetic Counselors.
For more information see Whole Exome and Genome Sequencing Information and Test Ordering Guide.
Shipping Instructions
Specimen preferred to arrive within 96 hours of collection.
Necessary Information
1. Whole Exome Sequencing: Ordering Checklist is required. Fill out one form for the family and send with the specimens.
2. Prior Authorization is available, but not required, for this test. If proceeding with the prior authorization process, submit the required form with the specimen.
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.
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
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 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: Cultured fibroblast
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 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: 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 fingerstick. For infants younger than 1 year, a heel stick should be used. See How to Collect Dried Blood Spot Samples 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)
Specimen Type: Saliva
Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.
Supplies: Saliva Swab Collection Kit (T786)
Specimen Volume: 1 Swab
Collection Instructions: Collect and send specimen per kit instructions.
Specimen Stability Information: Ambient 30 days
Additional Information: Due to lower concentration of DNA yielded from saliva, it is possible that additional specimen may be required to complete testing.
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. Whole Exome Sequencing (WESDX) Prior Authorization Ordering Instructions
4. If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.
Secondary ID
616068Useful For
Serving as a first-tier test to identify a molecular 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
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| G226 | Number of Comparators for WESDX | No, (Bill Only) | No |
| MATCC | Maternal Cell Contamination, B | Yes | No |
| CULFB | Fibroblast Culture for Genetic Test | Yes | No |
Testing Algorithm
If a cord blood specimen is received, maternal cell contamination testing will be added and performed at an additional charge.
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.
Special Instructions
- Whole Exome Sequencing: Ordering Checklist
- Blood Spot Collection Card-Spanish Instructions
- Blood Spot Collection Card-Chinese Instructions
- Blood Spot Collection Instructions
- Whole Exome Sequencing (WESDX) Prior Authorization Ordering Instructions
- Whole Exome and Genome Sequencing Information and Test Ordering Guide
Method Name
Sequence Capture and Targeted Next-Generation Sequencing followed by Sanger Sequencing or Quantitative Polymerase Chain Reaction (qPCR), as needed.
Reporting Name
Whole Exome SequencingSpecimen Type
VariesSpecimen Stability Information
| Specimen Type | Temperature | Time |
|---|---|---|
| Varies | Ambient (preferred) | |
| Frozen | ||
| Refrigerated | ||
Clinical Information
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 specimens 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.(3-5) However, testing for singletons (patient only), duos (patient and one family member to be used as a comparator), and non-traditional trios (patient and two family members to be used as comparators) will also be accepted if both biological parents are unavailable.
Reference Values
An interpretive report will be provided.
Cautions
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.
To discuss the availability of additional testing options or for assistance in the interpretation of these results, contact Mayo Clinic Laboratories genetic counselors at 800-533-1710.
Technical Limitations:
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.
If the patient has had an allogeneic hematopoietic stem cell transplant or a recent 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.
Reclassification of Variants:
Currently, it is not standard practice for the laboratory to systematically review previously classified variants on a regular basis. The laboratory encourages healthcare 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 are performed using published American College of Medical Genetics and Genomics and the Association for Molecular Pathology recommendations as a guideline (ACMG).(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 judgment.
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.
Day(s) Performed
Varies
Report Available
84 daysPerforming 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)
NY State Approved
YesPrior Authorization
Insurance preauthorization is available for this testing; forms are available.
Patient financial assistance may be available to those who qualify. Patients who receive a bill from Mayo Clinic Laboratories will receive information on eligibility and how to apply.