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Test Code LAB3796 Exome Sequencing (Send-out)

Clinical System Name

Exome Sequencing (Send-out)

Synonyms

Exome; WES; Whole Exome; Whole Exome Sequencing

Sample Requirements

Preferred Specimen: Whole Blood

Container: Lavender top (EDTA)

Preferred Vol: 5.0 mL

Minimum Vol: 3.0 mL

  • 1.0 mL may be acceptable for infants. Please contact Send Outs at ext. 7-2563 for confirmation of 1.0 mL minimum volume.

 

Specimen: Extracted DNA

Container(s): Sterile Plastic Tube

Preferred Vol: 5 µg at a concentration of ≥50 ng/µL AND a volume of ≥100 µL

 

Alternative Specimen(s): Please see Alternate Specimen Collection Kits for Genetic Testing for more information. Please contact Send Outs at referencelabteam@seattlechildrens.org or call us at ext. 7-2563 for additional questions regarding alternative specimen acceptibility.

Processing Instructions

Reject due to:

Spin: N

Aliquot: N

Temp:

  • Whole Blood or Extracted DNA: 2 - 8 C
  • Buccal Swabs or Saliva Swabs: RT

Storage Location:

  • CPA refrigerator, Send Outs rack.
  • Send Outs room temperature rack.

Off-Site Collection: Send whole blood refrigerated.

Stability

Specimen Type Temperature Time
Whole Blood Room Temp 3 d
  Refrigerated 7 d
  Frozen Unacceptable
Extracted DNA Room Temp 3 - 4 d
  Refrigerated 1 y
  Frozen Indefinitely
Buccal Swabs or Saliva Room Temp Ref Lab Dependent

Availability

STAT TAT
N 5 - 7 w

Performing Laboratory

This testing can be performed by any of the following laboratories:

  • GeneDx

207 Perry Parkway

Gaithersburg, MD 20877

Phone Number: (301) 519-2100

 

  • PreventionGenetics

3800 South Business Park Avenue

Marshfield, WI 54449

Phone Number: (715) 387-0484

 

  • UW Northwest Clinical Genomics Laboratory

1959 NE Pacific St

Seattle, WA 98195

Phone Number: (206) 685-1176

Department

Department: Send Outs/Genetic

Phone Number: (206) 987-2563

Reference Range

Interpretive report provided.

Send Out Instructions

Reference Lab Test Name:
  • XomeDx (GeneDx)
  • PGxome Diagnostic Exome Test (PreventionGenetics)
  • Exome Sequencing (UW NCGL)
Reference Lab Test Code:

XomeDx:

  • 561b (Proband w/o mtDNA)
  • 561e (Duo w/o mtDNA)
  • 561a (Trio w/o mtDNA)

XomeDx Plus

PGxome Diagnostic Exome Test:

  • 5000 (Proband)
  • 5200 (Duo)
  • 5300 (Trio)

Exome Sequencing at UW NCGL
Send-out Instructions:

GeneDx and PreventionGenetics: Ship Monday through Friday via FedEx Priority Overnight. Saturday deliveries are accepted.

 

UW NCGL: Send Monday through Friday with the UW courier (0700, 1400, or 2200). Attach a Pass Thru label to the temperature-appropriate UW biohazard bag. Write "UW NCGL" in the "To:" field and "SEACOH" in the "From:" field.

Special Instructions

GeneDx

Requisition

GeneDx

Test Info

 

PreventionGenetics

Requisition

Test Info

 

UW NCGL

Requisition

Test Info

Methodology

Method: Next-generation sequencing with CNV calling (NGS-CNV)

 

Coverage and limitations may vary between performing labs. See linked Test Info in the Special Instructions section for details.

 

If ordered, the mitochondrial genome is analyzed by NGS-CNV and alternative sequencing or other detection methods may be used to analyze or confirm mtDNA variants. Next generation sequencing of the mitochondrial genome can detect mtDNA variants as low as 2% heteroplasmy and large-scale deletions (2 kb or larger) as low as 5% heteroplasmy. However, for large-scale deletions observed at less than 15% heteroplasmy a quantitative value will not be provided. This test is expected to detect greater than 98% of known pathogenic variants and deletions of the mitochondrial genome.

 

This is a phenotype-driven test of a very large number of genes; therefore, reported results are focused on pathogenic variants, likely pathogenic variants, and variants of uncertain significance in genes related to the clinical information provided. 

Description

Exome Sequencing (Send-out) analyzes the nuclear exome at one of three performing laboratories: GeneDx, PreventionGenetics, and University of Washington Northwest Clinical Genomics Lab (UW NCGL).

 

This test evaluates the protein-coding regions (exons) of ~20,000 genes, which account for approximately ~2% of the human genome. Concurrent mitochondrial genome sequencing and deletion testing can be ordered at GeneDx.

 

Exome sequence analysis is performed on the affected individual (i.e., the proband) and, when submitted together for analysis, biological parental samples, and/or additional biological relatives as needed. Standardly, a report is issued only for the proband. If ordered, the mitochondrial genome sequencing and deletion test results are issued in a separate report.

Clinical Utility

Exome sequencing can be used to identify the underlying molecular basis of a genetic disorder in an affected individual with:

  • A constellation of clinical findings not recognized as part of a known syndrome
  • One or more congenital anomalies, dysmorphic features, or birth defects
  • Unexplained epilepsy
  • Unexplained hypotonia
  • Neurodevelopmental disorders including global developmental delay/intellectual disability, with or without dysmorphic features
  • A phenotype suggestive of a genetic etiology that does not correspond to a specific condition for which genetic testing is available
  • A suspected genetic condition that has a high degree of genetic heterogeneity
  • Unresolved genetic testing such as normal karyotyping or microarray analysis, and negative single gene or gene panel sequencing results

 

Reported diagnostic rates from commercial and academic laboratories have found that WES assays have a ~20-40% positive diagnostic rate, with higher rates being reported from trio analysis (i.e. proband and parents) compared to singleton analysis. Several large studies including those with critically ill infant populations have demonstrated that exome sequencing identifies a causal variant in 25-58% of cases, with a higher yield for cases that specifically include other biological family members.

 

Common features of mitochondrial disease may include ptosis, external ophthalmoplegia, proximal myopathy, exercise intolerance, cardiomyopathy, sensorineural deafness, optic atrophy, pigmentary retinopathy, diabetes mellitus, encephalopathy, seizures, dementia, migraine, stroke-like episodes, ataxia, spasticity, chorea and dementia. 

 

The combination of full sequence analysis plus deletion testing is expected to identify a mitochondrial DNA variant in approximately 40% of adults and 10-20% of pediatric patients with a primary mitochondrial disorder. 

 

A genetic diagnosis may have implications for treatment, management, recurrence risk, and family member testing.