Home
HelpTest Code 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.
-For detection of single nucleotide variants, small insertions and deletions, copy number variants, deep intronic variants, trinucleotide repeat variants, and mitochondrial genome variants, order WGSDX / Whole Genome Sequencing for Hereditary Disorders, 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 sequencing 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
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 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
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.
Specimen Stability Information: Ambient (preferred)/Refrigerated
Additional Information:
1. Blood spot specimens are acceptable but not recommended. Multiple extractions will be required to obtain sufficient yield for supplemental analysis, and there is significant risk for test failure due to insufficient DNA.
2. Due to lower concentration of DNA yielded from blood spot, 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.
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 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 skin or tissue biopsy. Cultured cells from a prenatal specimen will not be accepted.
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: Extracted DNA
Container/Tube:
Preferred: Screw Cap Micro Tube, 2mL with skirted conical base
Acceptable: Matrix tube, 1 mL
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.
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 1 of the following forms 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
Genetics Test Information
This test utilizes next-generation sequencing to detect single nucleotide and copy number variants within the protein-coding regions of approximately 20,000 genes. See Method Description for additional details.
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 specimens 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 two 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.
Prior Authorization is available for this assay.
Testing Algorithm
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
- Whole Exome Sequencing: Ordering Checklist
- Hereditary Peripheral Neuropathy Diagnostic Algorithm
- Blood Spot Collection Card-Spanish Instructions
- Blood Spot Collection Card-Chinese Instructions
- Epilepsy: Unexplained Refractory and/or Familial Testing Algorithm
- Blood Spot Collection Instructions
- Whole Exome Sequencing for Hereditary Disorders (WESDX) Prior Authorization Ordering Instructions
- Whole Exome and Genome Sequencing Information and Test Ordering Guide
Method Name
Sequence Capture and Targeted Next-Generation Sequencing (NGS) 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 | Varies | |
Reject Due To
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.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.
Interpretation
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.
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)
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.
Variants previously identified through testing performed at other laboratories via different methodologies, or different ordered services may or may not be re-reported in this analysis. The inclusion of such variants in the final report is at the discretion of the laboratory based on clinical relevance, current interpretation standards, and the context of the patient's phenotype. Variants may be re-reported using a different genome build and/or transcript that utilizes alternative nomenclature; similarly, reported breakpoints for copy number variant(s) may differ due to differences in testing methodologies.
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 opts out of this evaluation unless they overlap with the patient's reported clinical features.
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-causing or likely disease-causing variants in these genes, as portions of the genes may not be adequately covered by this testing methodology.
Reanalysis and Raw Data Requests:
Patient data is not guaranteed to be stored indefinitely. Requests for reanalysis or release of raw data may not be possible, and a new whole exome sequencing order may be required if the original patient data is no longer available or no longer compatible with current bioinformatics processes or analysis tools.
Healthcare professionals 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.
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.
Day(s) Performed
Varies
Report Available
56 to 70 daysSpecimen Retention Time
Whole blood: 28 days (if available); Extracted DNA: 3 months, Saliva: 30 days (if available; 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)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| WESDX | Whole Exome Sequencing | 86205-2 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 616410 | Interpretation | 69047-9 |
| 616411 | Specimen | 31208-2 |
| 616412 | Source | 31208-2 |
| 616413 | Released By | 18771-6 |
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 |
Prior 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.