Constitutional Whole Exome Sequencing (WES) for Undiagnosed Disease

Constitutional Whole Exome Sequencing (WES) for Undiagnosed Disease

Constitutional whole exome sequencing (WES) is a powerful genetic test intended for children or adult patients with an undiagnosed health condition that suggests an underlying genetic cause. This test involves targeted sequencing of all ~20,000 genes of the exome, the subset of genomic DNA that encodes proteins (known as exons), using high-throughput next-generation DNA sequencing technology.

NYGC’s clinical constitutional whole exome sequencing test is offered as a trio-test in which the affected patient of interest (proband) together with two first-degree relatives (usually the biological parents) are sequenced together. Sequencing data is analyzed in the context of family relationships to increase the likelihood of identifying genetic variants that may be contributing to the symptoms observed in the child. NYGC’s Clinical Laboratory also accepts samples from just the affected individual, as well as from other affected or unaffected relatives, as appropriate to provide additional context and help guide interpretation on a case-by-case basis.

Knowledge of disease-causing mutations is changing at a rapid pace. To help clinicians better serve their patients, NYGC’s proprietary WES pipeline incorporates up-to-date variant databases and disease-specific databases to keep pace with the ever-changing growth in knowledge. Additionally, WES may also identify variants in genes previously not linked to a disease (novel genes). Since WES interrogates all protein-coding regions, it replaces the potential need for multiple costly single-gene tests, avoids clinician guesswork or bias in gene testing decisions, improves the odds of identifying a high-risk variant and thereby improves diagnostic success rate and guidance of appropriate clinical management.


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NYGC’s Clinical Laboratory returns results within 4-6 weeks on a standard basis, but can provide more rapid turnaround if needed. Results are sent to the physician and/or genetic counselor (due to the complexity of genetic testing and potential implications of the test results) who then discuss the results with the patient. The results of this test can become part of the patient’s medical record.

A report will be provided indicating the variants that could explain the clinical phenotype. In addition, the Clinical Laboratory will report secondary findings in medically actionable genes as per the American College of Medical Genetics and Genomics (ACMG) guidelines. Patients will also be able to “opt in” to learning their carrier status for autosomal recessive genes recommended by the ACMG and the American Congress of Obstetricians and Gynecologists (ACOG) for reproductive screening.

An up-close image of scientific equipment with red and black wires in a lab

Ordering Instructions

A physician can order the test using NYGC’s test requisition form and must obtain informed consent from each family member (in pediatric cases, the child’s parents) being tested. This test requires at least 2ml of blood drawn in an EDTA tube or saliva specimen collected in an Oragene Dx collection kit or DNA extracted in a CLIA-certified laboratory from each family member being tested (all samples submitted together whenever possible). Samples should be shipped to NYGC overnight via FedEx. A courier service may also be feasible.