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Whole Exome Sequencing
Whole exome sequencing (WES) identifies changes in a patient's DNA by focusing on the most informative regions of the genome – the exome.
For certain patients the combination of symptoms does not allow the clinician to pinpoint a potential diagnosis. In such challenging cases, often a stepwise diagnostic strategy is chosen, which makes the testing complex, time consuming, costly and often not even conclusive. Furthermore, a delayed diagnosis may have a significant impact on the patient’s treatment and quality of life.
For these cases, the use of WES has advantages over initially more targeted genetic testing. Whereas such targeted genetic testing focuses on a single gene or on a limited set of predetermined genes, WES testing examines all the protein coding regions in the genome (exons) simultaneously. It is estimated that most of the disease-causing mutations (about 85%) are located within the exons. This lack of bias allows to also identify disease causing variants in genes that would be missed by targeted approaches.
CentoXome®, CENTOGENE’s whole exome sequencing service, offers an accurate and cost-effective one-step solution, with high diagnostic yield.
Why Choose CentoXome®?
CentoXome® – Key Features
| FEATURES | ||||||
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| COVERAGE |
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| VARIANTS | Reliable and sensitive detection of SNVs, InDels and CNVs
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*Typically, CentoXome® reaches 20x coverage or higher for 98.5% to 99.5% of targeted regions. However, the minimum guaranteed coverage for every CentoXome® sample is ≥98% of targeted regions ≥20x
**Variants with low quality and/or unclear zygosity are confirmed by an additional method
The CentoXome® offers a highly uniform coverage of the complete exome and detects simultaneously with high sensitivity single nucleotide variations (SNVs), small insertions/deletions (InDels) and copy number variations (CNVs) in a single test.
The inclusion of NGS-based detection of CNVs as default feature allows not only the detection of previously described CNVs throughout the exome but also de novo CNVs and small CNVs that might escape detection for example by chromosomal microarray analysis. This is possible due to the higher resolution of our NGS-based CNV analysis.
My positive diagnostic rate has gone up from 15% using just CGH microarray to 80% using targeted sequencing and whole exome sequencing. I am now able to do proper, informed genetic counselling.
When is WES Recommended?
For many patients with suspected genetic conditions the combination of symptoms does not allow suspecting specific genetic causes with a sufficiently high certainty. It is unclear which genes to look at.
Therefore, WES may be an affordable first test when the clinical spectrum is diverse and diagnostic answers are likely to be obtained only through sequencing the complete coding region, i.e. the whole exome. WES is also a good follow-on approach after more targeted approaches have been tried already and no causative variant was identified.
We particularly recommend CentoXome® for patients:
- With clinical or genetic heterogeneity
Examples: Epilepsy, epileptic encephalopathies, muscular dystrophies/muscular disorders, ataxia, neuropathies, cardiomyopathies, skeletal dysplasias, immunodeficiency, deafness, blindness
- With atypical clinical presentations or phenotypes
Example: A patient presenting with intracranial aneurysm (due to PKD1 gene - polycystic kidney disease)
- With “blended” clinical presentations and clinical suspicion of dual diagnosis
Examples: Intellectual disability and severe immunodeficiency
- With clearly genetic disease, but previous genetic testing having been negative.
Example: A patient with autosomal dominant spastic paraplegia and with a negative result for the gene panel
- Who are critically ill and a rapid diagnosis is a medical necessit
Example: First-line test for diagnosing rapidly critically ill newborns or children hospitalized in neonatal (NICU) or pediatric intensive care (PICU) to guide timely and appropriate clinical management
- Who need a cost-conscious alternative to whole genome sequencing
Downloads for whole exome sequencing
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CentoXome® - Case study
DownloadPatient diagnosed with primary coenzyme Q10 deficiency type 4 after detecting two pathogenic variants in the COQ8A gene. This ended the diagnostic odyssey, allowed appropriate treatment, and helped the patient and his partner with preconception counseling.
CentoXome® – Tailored Services to Your Patient's Needs
| OPTIONS AND PACKAGES | ||
|---|---|---|
| Turnaround time | Regular | ≤30 business days |
| Fast | ≤15 business days | |
| Testing design | Solo, Duo, Trio, and Trio Plus | |
| Additional testing options | High resolution analysis of structural variants (SVs)/large CNVs with CentoLCV, CentoArrayCyto® 750K or HD | |
Mitochondrial genome analysis with CentoMito® Genome | ||
Reanalysis and medical reinterpretation at low cost in case of uncertain or negative results | ||
Prenatal with prioritization and expediting at each stage of the process*
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* Please consult our dedicated Prenatal Testing page for details
We provide different options and additional services to tailor the CentoXome® analysis to your patient’s needs, which improves even more the clinical utility of CentoXome® for the patients we test in our laboratory.
The test results from CentoXome® may also lead to more rapid diagnoses, improved prevention of symptomatic illness, more targeted treatments or even end the need for some costly or invasive procedures.
For example, CENTOGENE showed in a peer-reviewed publication that WES, specifically CentoXome®, can find timely diagnostic answers for more than half of patients with rare and undiagnosed conditions1. The results demonstrated also that WES is a low-cost and efficient first-tier genetic analysis in patients with non-specific and/or heterogeneous phenotypes, emphasizing the clinical benefit of WES in light of facilitation of personal medical care.
Conclusive Clinical Reports
High-quality reporting is an essential element for building a partnership of trust. Our philosophy is more than just producing technical data. The extensive interpretation of clinical and testing data delivered with our comprehensive medical reports includes differential diagnostic approaches as well as a detailed interpretation of key findings.
CENTOGENE’s large proprietary rare disease data repository, CentoMD®, that includes the systematic documentation of curated genetic variants, with detailed clinical information, frequency and geographic origin, coming from a worldwide cohort of patients, strongly strengthens the clinical interpretation of our CentoXome® results and warrants best diagnostic yields. It significantly improves the quality and consistency of the diagnosis, ultimately affecting your patients' treatment path.
- Detailed evaluation of patient’s clinical information and family history
- Comprehensive data and medical interpretation by experienced professionals
- Clear results of identified variants that can explain the phenotype following international best-practice guidelines (ACMG)2,3
- Recommendations for differential diagnoses or follow-up analyses for specific diseases
- References to publications supporting the medical and scientific results
- Detailed method description
- Optional research findings related to phenotype if the diagnostic results are negative, and/or incidental findings based on the ACMG guidelines3
- CENTOGENE’s 'Tabular List' variant section, which includes known gene variants in CentoMD® that have been classified pathogenic/likely pathogenic and are linked to severe and early-onset diseases (for more information, see details and the list of genes covered).
Clinical anamnesis
One consequence of WES is the increased amount, complexity, and variety of results that need to be interpreted. Therefore, it is of utmost importance to obtain specific and detailed clinical information from the index patient and the parents when performing exome sequencing.
Withholding any clinical information, including your patient's family history, may affect test results and their interpretation. Several studies have shown that the chances of having a clinically useful genetic result increases with the quality of the clinical information provided.1,4 For example, the CentoXome® diagnostic yield improved from about 26% when using few clinical information to about 40% as compared when we received detailed clinical information.1
REFERENCES: 1Trujillano et al. 2017, PMID: 27848944; 2Richards et al. 2015, PMID: 25741868; 3Kalia et al. 2017, PMID: 27854360; 4Köhler et al. 2019, PMID: 30476213
Scientific articles
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Genetic Cause of Impaired Neurodevelopment
Development of the nervous system is a complex process, with NEUROG1 being one out of many genes involved. The critical role of this gene was recently confirmed by CENTOGENE, when a patient with disturbed neurodevelopment was observed as having the gene knocked out. The finding was published in…
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A Rare Genetic Disease in Which Symptoms Naturally Improve
While most genetic disorders progress from mild to severe, a certain form of muscle disease was suggested to represent an exception. However, this was based on observations in only two patients. As a result of identifying three additional patients, scientists at CENTOGENE have now been able to…
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Disturbed Growth Signaling Linked to a Novel Disorder
Most studies that report novel gene-disease associations lack functional insights. A recent exception is a high impact paper on a skeletal dysplasia caused by recessive variants in SCUBE3. In a global collaborative effort involving researchers from CENTOGENE, a specific signaling pathway could be…