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)

This test is only appropriate for patients who have had hereditary panel testing performed on a postnatal sample via next-generation sequencing (NGS) utilizing the Integrated DNA Technologies chemistry performed by Mayo Clinic Laboratories. To confirm that this test is possible for a specific patient, contact the laboratory at 800-533-1710.

If the patient has not had an appropriate test previously performed by Mayo Clinic Laboratories that can be reflexed but whole exome sequencing is desired, order either WESDX / Whole Exome Sequencing for Hereditary Disorders, Varies or WESMT / Whole Exome and Mitochondrial Genome Sequencing, Varies. If whole genome sequencing is desired, order WGSDX / Whole Genome Sequencing for Hereditary Disorders, Varies. A new specimen may be required.

This test is for affected patients (probands) only. It is possible to add family member comparators. For family member specimens being sent as comparators, order CMPRE / Family Member Comparator Specimen for Exome Sequencing, Varies. If WESPR is ordered on a family member comparator, this test will be canceled and CMPRE added as the appropriate test.

This test cannot support detection of deep intronic variants, trinucleotide repeat variants, or variants in the mitochondrial genome.

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. A new specimen may be required.

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. A new specimen may be required.

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

Patient DNA is required to allow for confirmation of any new reportable variants, based on internal laboratory criteria. For most patients, stored DNA from the original panel test should be available for this testing. If a DNA sample is depleted or discarded, testing will proceed, however, a new sample will be requested from the ordering provider to attempt any necessary confirmatory testing. If a new sample is not provided, any findings that require confirmation will be reported with a disclaimer that confirmation was not performed due to lack of a DNA specimen.

To order whole exome sequencing for the patient and family member comparator specimens after a negative or inconclusive hereditary next-generation sequencing gene panel performed at Mayo Clinic Laboratories, perform the following steps:

1. Order WESPR / Panel to Whole Exome Sequencing Reflex Test, Varies

2. Call Mayo Clinic Laboratories at 800-533-1710 to request that the remaining DNA specimen be added to the WESPR order.

3. Complete the required paperwork and informed consent: Whole Exome Sequencing: Ordering Checklist.

4. Attach clinic notes from specialists relevant to patient's clinical features, if available.

5. Attach pedigree, if available.

6. If submitting family member comparator samples, order CMPRE / Family Member Comparator Specimen for Exome Sequencing, Varies for each family member.

 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, non-first-degree 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.

7. If needed, collect specimens. Label specimens with full name and birthdate. Do not label family members' specimens with the proband's name.

8. Send paperwork to the laboratory along with the specimens. If not sent with the specimen or if no specimen is being sent, 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.

Necessary Information

Whole Exome Sequencing: Ordering Checklist is required. Fill out one form for the family and send with the specimens or fax to 507-284-1759, Attn: WES Genetic Counselors.

Specimen Required

For most patients, a new specimen submission will not be required. Testing can be performed using stored DNA from the original whole exome sequencing test. To order testing on the stored specimen, see Additional Testing Requirements.

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: Lavender top (EDTA) or yellow top (ACD)

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 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 samples 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 is met, the preferred volume of blood must be submitted. Testing may be canceled if DNA requirements are inadequate.

Specimen Type: Cord 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 specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 4 days

Additional Information:

1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for samples received after 4 days and DNA yield will be evaluated to determine if testing may proceed.

2. 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: 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 is required to culture fibroblasts before genetic testing can occur.

Specimen Type: Cultured fibroblasts

Source: Skin

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) <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 is required to culture fibroblasts before genetic testing can occur.

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 (formally Ahlstrom 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 Dried Blood Spot Samples.

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, 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: Saliva

Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.

Supplies: Saliva Collection Kit (T786)

Specimen Volume: 1 Swab

Collection Instructions: Collect and send specimen per kit instructions.

Specimen Stability Information: Ambient (preferred) 30 days/Refrigerated 30 days

Additional information: 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.