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Test Code WES Whole Exome Sequencing, Varies

Advisory Information

This test is only available for trios (proband, biological mother, and biological father).


Clients must provide all 3 samples for this test to be performed; each specimen must be on a separate order for WES / Whole Exome Sequencing.


Additional Testing Requirements


Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

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 the whole exome sequencing genetic counselors at 507-284-0670.

Specimen Required

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


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 inadequate.

Useful For

Identifying 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


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


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

Testing Algorithm

Whole blood samples must be collected from the patient's biological parents and are required for the analysis of the patient's results. Analysis of these samples is included in the list price for the patient's test and additional charges will not be applied to the parental samples.


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) Patients may opt-out of receiving these test results.


Complete the Patient Information and Informed Consent forms and send to the laboratory along with the specimen. The forms are located within the Whole Exome Sequencing: Ordering Checklist, Patient Information, and Informed Consent forms in Special Instructions. The completed forms may also be faxed directly to the whole exome sequencing genetic counselors at 507-284-0670.


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


Sanger sequencing may be performed for verification of results.


The following algorithms are available in Special Instructions:

-Inherited Motor Neuron Disease Testing Algorithm

-Epilepsy: Unexplained Refractory and/or Familial Testing Algorithm

-Neuromuscular Myopathy Testing Algorithm

-Hereditary Peripheral Neuropathy Diagnostic Algorithm

Method Name

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

Reporting Name

Whole Exome Sequencing

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

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 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 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 patient)

-Patient 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)

-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.

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).


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.


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

Day(s) and Time(s) Performed

Performed weekly, Varies

Analytic Time

12 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

Codes Applied to Proband Sample:


81416 x 2

LOINC Code Information

Test ID Test Order Name Order LOINC Value
WES Whole Exome Sequencing 86205-2


Result ID Test Result Name Result LOINC Value
113160 Interpretation 69047-9