MNG Healthy Exome™
Healthy Whole Exome Sequencing (HWES)
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.
Whole Exome Sequencing (WES)
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 thus it has a higher chance to find the cause of a heritable disease. WES 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 genetic variant has been identified, this information can then be linked back to the phenotype of the patient, which will improve the pathway to a correct diagnosis and a suitable treatment plan can be developed.
The MNG Exome™ includes copy number analysis and mitochondrial genome sequencing & deletion analysis
The MNG ExomeTM 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. Copy number and uniparental disomy are now being detected with our coverage and analysis pipeline. We prefer to test trios but also offer proband-only tests if parents or other 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 NGS 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 required for establishing the correct genetic diagnosis.
Data analysis is performed by our Genome MaNaGer™ pipeline described below. All disease-causing variants are confirmed using an alternative technology before reporting. Our turnaround time is 2-4 weeks. 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.
Genome MaNaGer™ Pipeline
The value of Next Generation Sequencing depends on the sensitivity and specificity of the testing as well as clear, user-friendly interpretation and reporting of results. We focus on identifying the cause of the disease and only report mutations that are either certain or likely to cause the condition based on available scientific evidence. Our unique approach and proprietary process to evaluating the significance of genetic changes centers on the concept of genetic disorders as diseases of molecular systems, rather than only looking at individual genes.
We also improve our decision-making by including functional information about genes obtained from model organisms. Our proprietary database incorporates this “system related phenotype interpretation” approach into our analysis and thus ensures delivery of first-in-class specificity and sensitivity in our reporting.
Our analytical pipeline automatically monitors all important quality metrics to assure robust and reproducible results. These include the total number of reads obtained, percentage of reads mapping to the desired target regions, the completeness of the coverage for regions of interest (guaranteed greater than 99%). In addition, we monitor the transition-to-transversion ratio among the variants detected, the ratio of homozygous to heterozygous changes, as well as the ratio of low confidence calls to high confidence calls.
Gender is independently established from the ratio of heterozygous and homozygous calls on the X chromosome; we also monitor the percentage of rare variants shared between the proband and additional tested family members to ensure sample and familial connection. For this same reason we also confirm all disease causing mutations with an independent methodology using the original DNA sample.
Certifications and Reporting
MNG adheres to the strict guidelines of CLIA, CAP and ACMG. Our reports focus on single nucleotide changes and small (<100bp) insertions and deletions found in the exome and mitochondrial DNA. We can report incidental findings based on ACMG guidelines if the patient or the patient’s guardian chooses to receive such results. We do not report carrier status, parental data, copy number changes, or repeat expansion disorders. We can offer a reevaluation of our reports upon request. Whole exome sequencing requires the submission of a signed consent form. The consent form must be signed by all parties.
MNG Laboratories Offers Flexibility and Attractive WES Testing
WES001: MNG Exome Trio Sequencing + mtDNA sequencing for proband and mother
Proband + up to 2 family members. Trios are preferred for better diagnostic sensitivity. mtDNA is analyzed for the proband even if the mother’s DNA is not available.
TAT: 2-4 Weeks
WES002: Additional Family Member
One or more additional family members can be included when ordering (WES001) to increase the probability of establishing the correct diagnosis by ordering WES002 at the same time. Depending on findings in the trio, mtDNA may also be used to help in interpreting and reporting.
TAT: 2-4 Weeks
WES003: MNG Exome Proband Only Sequencing + mtDNA
Sometimes only the proband is available for testing and MNG will accept proband only orders under WES003 when parental or other family member samples are not available.
TAT: 2-4 Weeks
MNG Exome™ Comparison Chart
Does not include Rapid TAT Exomes, based on posted data March 2017.