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Test Code LAB3432 Rapid Whole Exome Sequencing + mtDNA Seq

Important Note

This test is only available to Seattle Children's patients and must be ordered in coordination with a genetics provider. Please contact the Laboratory Genetic Counselor team at LabGC@seattlechildrens.org with questions.

Clinical System Name

Rapid Whole Exome Sequencing + mtDNA Seq

Sample Requirements

Preferred Specimen: Whole Blood

Container: Lavender top (EDTA)

Preferred Vol: 6.0 mL

Minimum Vol: 3.0 mL

  • Note: 1.0 mL is acceptable for infants if a higher volume is not possible.

 

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: Buccal Swab

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 90 d

 

Availability

STAT TAT
N Verbal result in 7 d, Final report in ~ 2 w

Performing Laboratory

GeneDx

207 Perry Parkway

Gaithersburg, MD 20877

Phone Number: (301) 519-2100

Department

Department: Send Outs/Genetic

Phone Number: (206) 987-2563

Reference Range

Interpretive report provided.

Send Out Instructions

Reference Test Name:

XomeDxXpress + Mito Genome Sequencing & Deletion Testing
Reference Lab Test Code:

896 + 690c
Instructions:

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

Special Instructions

Requisition

GeneDx

Test Info Sheet (rapid nuclear exome)

Test Info Sheet (mitochondrial genome)

Methodology

Method: Next-generation sequencing with CNV calling (NGS-CNV) of the nuclear exome and mitochondrial genome. Alternative sequencing or other detection methods may be used to analyze or confirm mtDNA variants.

 

Across the exome, the average depth of coverage is 100-120x. It is anticipated that approximately 98% of the targeted region of an affected individual’s exome will be assessed at a minimum of 10x coverage, the minimum read depth necessary to detect a variant.

 

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 and likely pathogenic variants in genes related to the clinical information provided. Less frequently, variants of uncertain significance in candidate and differential diagnosis genes are reported.

Description

Rapid Whole Exome Sequencing + mtDNA Seq analyzes the nuclear exome and mitochondrial genome with an expedited turnaround time.

 

This test evaluates the protein-coding regions (exons) of ~20,000 genes, which account for approximately ~2% of the human genome, and includes concurrent mitochondrial genome sequencing and deletion testing.

 

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. A report will be issued only for the proband. 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:

  • One or more congenital anomalies
  • Unexplained epilepsy
  • Unexplained hypotonia
  • Neurodevelopmental disorders including developmental delay
  • 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

 

The clinical sensitivity of exome sequencing depends, in part, on the proband's clinical phenotype. 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.