About Whole Exome Sequencing
Whole Exome Sequencing (WES) is a genetic test used to identify a heritable cause of a disorder. WES searches through all coding regions of all genes currently identified, yielding a high chance of finding the cause of a heritable disease. Whole exome testing can be used if a patient has symptoms which cannot be linked to a diagnosis and corrective treatment is desired to improve a patient’s prognosis. Once a pathogenic variant has been identified, this information can then be linked back to the phenotype of the patient to clarify the pathway to a correct diagnosis and the development of a suitable treatment plan. We offer two whole exome sequencing tests, the MNG Exome™ and the MNG Healthy Exome™.
The MNG Exome™ is a comprehensive exome sequencing test that searches through the protein coding region of all currently identified genes for disease-causing single nucleotide variants (SNVs), indels, and copy number changes. This test is used in situations where a patient’s symptoms are hard to classify in a single disease category.
The test is based on the Agilent SureSelect Human All Exon V6, a high performing design that targets updated content, including challenging regions, from the databases relevant to both clinical and translational researchers. Our target is 200 fold average coverage and we guarantee a 160 fold average coverage, allowing assessment of greater than 99% of targeted regions. The depth-of-coverage and high reproducibility of our capture and sequencing methodologies allow for the identification of copy number changes through the Genome MaNaGer® analysis pipeline. Our MNG Exome™ covers all pathogenic variants that are practice guideline and expert panel reviewed by ClinVar. These include variants located in intronic regions that are not covered by standard exome sequencing.
Copy number and uniparental disomy are now being detected with our sequencing coverage and data analysis pipeline. We prefer to test trios but also offer proband-only tests if parents or other potentially informative relatives are not available for testing.
In addition to sequencing the nuclear exome of the proband and additional family members, we also include analysis of mtDNA using long-range PCR amplification and next-generation sequencing of the mitochondrial genome for the proband as well as the mother. If the mother of the proband is not available for testing, the proband mtDNA will still be analyzed. Testing for additional family members is also available if it is required for establishing the correct genetic diagnosis.
All disease causing mutations are confirmed using an alternative technology before reporting. It is important to note that the test currently does not report trinucleotide repeat expansions or genomic rearrangements. We also do not report out carrier status for the proband for diseases unrelated to the condition for which testing is ordered. Whole exome sequencing requires the submission of a signed consent form. The consent form must be signed by all parties.
MNG Carrier Exome™
MNG Carrier Exome™ is a novel, complete approach to determining carrier status for recessive disorders in prospective parents. This comprehensive test is designed to detect rare, family or sub-population specific variants that could have a deleterious effect in offspring. Rather than focusing solely on known pathogenic variants that are common in well characterized populations, the MNG Carrier Exome™ provides a wider range of coverage for those seeking a more thorough review versus standard carrier screening tests. It is not recommended for diagnostic purposes.
Whole exome sequencing is performed on both partners in order to detect shared known pathogenic and predicted disruptive variants in genes that are causative of autosomal recessive disorders.
A single report will be generated containing the known pathogenic and predicted disruptive variants in genes that are predicted to be disrupted in both future parents. The exception to this rule is pathogenic variants in certain sex chromosome encoded genes, or genes that are silenced based on parental origin. The reason for this exception is that in such cases the offspring can still manifest serious symptoms even if only one of the healthy future parents carries the variant.
MNG Healthy Exome™
The MNG Healthy Exome™ provides a whole exome sequencing and copy number assessment of an individual’s genome for advanced screening for individuals who wish to know their carrier status or predisposition for severe genetic disorders. This test is intended for asymptomatic individuals who want to use this information for family planning, preventing the development of life threatening diseases, or aid with their early detection and prognostication.
Whole exome sequencing is performed in order to detect known pathogenic and predicted disruptive variants in genes that could have a deleterious effect in offspring or in the tested individual later in life. Variants of uncertain significance and benign/likely benign variants are not reported. This test is not recommended for individuals with manifesting/symptomatic genetic disorders.
MNG Laboratories is committed to a patient-centered testing menu, high-quality diagnostics, and first-in-class reporting driven by our Genome MaNaGer® analysis pipeline. Our Neurogenetic Answers™ reporting process helps us stay at the forefront of the evolving genetics field with our regularly-updated NGS panels. Our team-based approach to variant assessment ensures we provide you with the variants that cause or are likely to cause disease and keep the number of variants of unknown significance to a minimum. Our comprehensive approach to diagnostics is accompanied by a team of customer support and scientific personnel available to answer your questions regarding our process, technology, and reports. Please contact us to learn more about how we may serve you and your patients.