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Test 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 MITON / Mitochondrial Nuclear Gene Panel, 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.



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


Specimen preferred to arrive within 96 hours of collection.



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 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 specimen in original tube.

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 fibroblasts

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 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. 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).


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:

-Neurology Specialty Testing Client Test Request (T732)

-Biochemical Genetics Test Request (T798)

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.

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

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.

 

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.

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)

Reporting Name

Exome and Mitochondrial Genome

Specimen Type

Varies

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Ambient (preferred)
  Frozen 
  Refrigerated 

Reject Due To

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.  

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. Separate test reports will be issued for WESDX / Whole Exome Sequencing for Hereditary Disorders, Varies and MITOP / Mitochondrial Full Genome Analysis, Next-Generation Sequencing (NGS), Varies.

 

For whole exome sequencing, 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)

 

For mitochondrial variants, the degree of heteroplasmy of each single nucleotide or delin (deletion-insertion) variant, defined as the ratio (percentage) of variant sequence reads to the total number of reads, will also be reported. Large deletions will be reported as either homoplasmic or heteroplasmic, but the degree of heteroplasmy will not be estimated, due to possible preferential amplification of the smaller deletion product by long-range polymerase chain reaction.

 

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.

 

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 selects to opt out of this evaluation, unless they overlap with the patient's reported clinical phenotype.

 

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-associated or likely disease-associated variants in these genes, as portions of the genes may not be adequately covered by this testing methodology.

 

Exome Reanalysis:

Healthcare providers 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.

 

Raw Data Requests:

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

84 days

Performing Laboratory

Mayo Clinic Laboratories in Rochester

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