Whole Exome Sequencing

Whole exome sequencing (WES) technology looks at all the coding regions of an individual’s genome, examining thousands of genes simultaneously. WES techniques put the results of these analyses in the context of an extensive mutation database of rare diseases, family, and patient medical histories and, ideally, parent exome sequencing results. For this reason, WES is one of the best methods of detecting the causal mutation in complex genetic conditions, as well as identifying new mutations.

LifeLabs Genetics offers life-changing laboratory testing to Canadians as soon as it becomes practically, commercially, and qualitatively available. LifeLabs Genetics offers the WES service in partnership with CENTOGENE, a world-class genetics company focused on rare diseases. As a result of this partnership, the WES service has the following features:

• Analyzes ~60 Mb of coding exons from >20,000 genes
• NGS sequencing of all exons, including exon/intron boundaries (10 bp into intron), relevant promoter regions, and all HGMD described pathogenic variants
• End-to-end bioinformatics analysis of raw data, including variant annotation and phenotypic information
• Automatic reclassification of variants with every update of our database
• Customer service, ordering, interpretation assistance, and logistics support to Canadian standards

WES leads to diagnosis, valuable prognostic information, individualized treatment (if condition is treatable), and productive conversations. In several large studies, WES provided a diagnosis in 30% of index cases, with an even higher yield when family members were tested.

• Family history record (phenotype) that suggests a genetic disorder
• Undiagnosed or misdiagnosed disease
• Medical answers likely available only by sequencing the whole exome
• Suspected presence of genetic (Mendelian) disease (X-linked or autosomal recessive and dominant inheritance)
• No focused genetic test available to target the suspected disease-causing gene
• Need a pre-conception and prenatal screening for a person with undiagnosed complex disease
• Requires more targeted care for such conditions as:
  • Epilepsy
  • Neurodevelopmental disorders
  • Bone diseases
  • Metabolic disorders
  • Cardiomyopathy
  • Complex dysmorphism
  • Severe Combined Immunodeficiency (SCID)
  • Immunological disorders
  • Dementia
  • Metabolic disorders
  • Autism
  • Blindness

• Standard, high quality, gold service turnaround time is 4-6 weeks
• Platinum, express service turnaround time is 3 weeks
• Timing estimates do not include time required for physician appointments, requisitions, consent signatures, sample collection, or courier/shipping times (samples are analyzed in Germany)

• Helps to pinpoint diagnoses and solve complex medical cases
• Looks at disease-causing mutations instead of relying on outward physical symptoms
• Examines thousands of genes simultaneously, instead of focusing on a single gene or gene set
• Offers a fast, cost-effective, one-step solution that may eliminate the need numerous batteries of tests
• Provides different levels of analyses based on family cooperation levels and budgets
• Compares a patient’s mutation results to over 100,000 others for reliable results
• Facilitates better tailored treatments and therapies
• Reveals the potential for passing on diseases to the next generation

Reports are sent to physicians only. LifeLabs Genetics will not share results directly with patients. The ordering physician will receive an email when results become available. Results are never shared via email; results will be made available on the CENTOGENE portal for viewing and downloading. Sample Report

Results documentation includes one of the following:

• Positive result: Identification of the mutation (genetic change in DNA known to cause the disease) in a gene that has been associated with the symptoms. This is the most straightforward result and can be used to test other family members to determine their risk of developing the same disease.
• Unclear result: The test found a mutation in a gene. Although the gene is known to be associated with a disease, the association between the disease and this specific mutation within the gene is unknown. For the interpretation of the test results, it is important to obtain specific and detailed clinical information from you and your family members (usually the biological parents) when performing exome sequencing.
• Negative result: No genetic changes are identified. This result does not necessarily mean that the cause of the disease is not due to an underlying genetic condition. It is still possible that there is a mutation in a region of the exome that is not covered by this type of exome sequencing analysis. If the results are negative, your physician or genetic counsellor may discuss the possibility of additional testing.

Reports will not be issued for the parents unless prior arrangements are made.

This test does not identify your ancestry.

National WES requisition form [PDF; 248 KB]

Ontario MOHLTC application form [PDF; 95 KB]

Centogene MDaid brochure [PDF; 701 KB]

Incidental Findings

LifeLabs Genetics and CENTOGENE adhere to the “ACMG Recommendations for Reporting of Incidental Findings” and will not report on findings not directly related to the cause of a disease and not listed in the ACMG guidelines. However, it does mean that we will report variants detected in certain genes that are outlined in these recommendations as being medically actionable. If you would prefer not to receive this information in your report, it is possible to opt out of this service.