Whole genome sequencing (WGS) identifies almost all changes in a patient’s DNA by sequencing both the entire protein-coding and the non-coding regions of the genome.
Today there are millions of patients suffering from misdiagnosed or undiagnosed genetic diseases as a result of incomplete genetic testing. Although in certain cases approaches like single gene testing, panel testing, or microarrays can identify the cause of a disease, these analyses are ultimately limited and can fail to reveal the full genetic cause. WGS, in contrast, overcomes such limitations and is the only test that can detect nearly all types of disease-causing genetic variants in one single test.1,2
Most studies on genetic diseases have been heavily biased towards variants in gene coding regions, but this only accounts for approx. 1–2% of a patient’s entire genome. Recently, however, a growing body of studies have demonstrated that clinical WGS offers a more comprehensive analysis than WES and can provide molecular diagnosis where WES can not.1-5 Key pathogenic variants lying outside gene coding regions are growing in number and importance. The spectrum spans from simple sequence variants to complex structural variants.5,6
CentoGenome, CENTOGENE’s whole genome sequencing service, offers the most comprehensive one-step solution with the highest diagnostic yield.
Why Choose CENTOGENE?
Distinctive product offering centered around high-quality genetic testing
Strong presence in and access to countries with a high prevalence of rare diseases
CentoCard provides easy logistics for central testing
Rare disease-centric Bio/Databank generates best-in-class medical insights
Deep expertise in rare, metabolic, and neurodegenerative diseases, as well as multiomics enables better diagnostics
Best-in-class insights powered by the CENTOGENE Biodatabank, curated by our team of scientists and medical experts.
Your Questions Answered
Unparalleled genome coverage and diagnostic power in a single test, providing fast-track to diagnosis and optimized therapies
Life-long support by a team dedicated to improving the lives of patients with rare diseases
CentoGenome offers unparalleled genome coverage and captures the broadest spectrum of disease-causing genetic variants in a single test. Our WGS solution is a highly effective diagnostic tool – delivering high diagnostic yields across a variety of rare genetic conditions.5,7
CentoGenome is especially valuable in patients for whom previous WES produced negative results, with a recent study showing its ability to solve up to 30% of WES negative cases.5
By choosing this comprehensive and rapid analysis, you can save valuable time to diagnosis for your patients and consequently may help to further refine prognosis and enhance therapeutic decision-making.
Features & Performance
|Highly uniform genome and mitochondrial genome coverage|| |
|Advanced detection of nearly all types of variants in one single test||Highly sensitive and specific detection of SNVs, InDels, SVs including CNVs, and mtDNA variants with heteroplasmy ≥15% |
SNVs: single nucleotide variants; InDels: small insertions/deletions; CNVs: copy number variations; SVs: structural variants; mtDNA: variants in mitochondrial DNA;
*Variants with low quality and/or unclear zygosity are confirmed by orthogonal methods (i.e., SNVs and InDels by Sanger sequencing; CNVs by Multiplex ligation-dependent probe amplification, MPLA; quantitative polymerase chain reaction, qPCR; or chromosomal microarray, CMA)
WGS is recommended especially for the diagnosis of patients with heterogeneous phenotypes, unclear or atypical clinical symptoms, or with a long list of prior differential diagnoses, or who have exhausted other genetic testing options. Recent studies and Medical Genetic Society Statements and Recommendations on clinical WGS support it as a first- or second-line diagnostic test when a patient’s symptoms or family history suggests a genetic cause of the diseases.8-12 This is especially the case when the clinical diagnosis is associated with a high level of genetic heterogeneity and when WGS results in a relevant clinical improvement and/or is a more cost-effective approach. For example, the ACMG (American College of Medical Genetics and Genomics) recommends the use of exome/genome sequencing as first-tier test for children with intellectual disability, developmental delay, or multiple congenital anomalies.11 We particularly recommend CentoGenome for patients in the following cases:
The symptoms are very broad, complex, or unspecific, not pointing towards specific disease or typical phenotype, as:
- Clinical or genetic heterogeneity (e.g., intellectual disability/developmental delay, epilepsy, muscular dystrophies/muscular disorders, ataxia, neuropathies, cardiomyopathies, skeletal dysplasias, immunodeficiency, deafness, blindness)
- Diseases or patients with atypical clinical presentations or phenotypes (e.g., patient with intracranial aneurysm due to PKD1 gene – polycystic kidney disease)
- Patients with 'blended' clinical presentations and clinical suspicion of dual diagnosis (e.g., patient with deafness and ichthyosis, intellectual disability and severe immunodeficiency)
- Suspicion of a microdeletion or microduplication syndrome (e.g., patients with neurodevelopmental delay, multiple dysmorphisms and/or malformations, growth delay)
- Suspicion of a mitochondrial disorder (e.g., patient with muscular weakness, cardiomyopathy, visual problems)
Prior testing did not provide a conclusive diagnosis, like:
- Patient with autosomal dominant spastic paraplegia, but a negative result for the gene panel
- Patient with neurodevelopmental delay and similarly affected siblings, but a negative testing with microarrays and WES
- Any case where a genetic disorder is suspected but WES is negative
A fast diagnosis is a medical necessity and there is not always the time for serial testing strategies, as seen with:
- Patients severely ill for whom a diagnosis may direct or alter medical management (e.g., children with seizures, hypotonia, neurological abnormalities, and a rapidly deteriorating clinical status)
- Newborns, babies and children where a rapid diagnosis is crucial for prognosis and treatments decisions (e.g., critically ill newborns and children in the neonatal and pediatric intensive care, NICU and PICU)
Our most recent study, where we present the largest cohort of patients with WGS performed in a clinical setting to date, demonstrated the diagnostic strength of CentoGenome as the most comprehensive genetic test and its superiority to WES.5 The results also support that WGS should be considered the 'standard of care' for genetic testing, as well as a first-line stand-alone test for rare disease patients.
CentoGenome helps you tackle challenging and undiagnosed patient cases across all stages of life.
CentoGenome covers a broad spectrum of disorders encompassing >7,000 rare diseases.
Tailored Services to Your Patient's Needs
We offer flexible testing options that allow you to tailor CentoGenome to your patient's needs:
- CentoGenome Prenatal - WGS for ongoing pregnancies with fetal abnormalities
- CentoGenome MOx - multiomic WGS that integrates deep genomic and biochemical insights in a single test
When a rapid diagnosis is a medical necessity
A rapid diagnosis can be critical for timely and appropriate medical intervention. Several recent studies demonstrate how the high diagnostic yield and short turnaround time of WGS enables improved clinical decision making in critically ill newborn infants and children in the Neonatal Intensive Care Units (NICU) or Pediatric Intensive Care Units (PICU).13-17 CentoGenome, with a turnaround time of down to 15 days, acts as a comprehensive and accurate tool that will potentially improve critical decision making when used as a first-line test for diagnosing critically ill newborns or children
Committed to Improving the Lives of Patients With Rare Diseases
CentoGenome includes life-long diagnostic support through (a) proactive, free-of-charge variant reclassification and (b) affordable case-level reanalysis for uncertain or negative results.
Due to the rapid rate of new gene-disease discoveries, it is estimated that 10-20% of uncertain or negative cases can be diagnosed by reclassification and reanalysis.18,19
Options & Additional Services
|Turnaround time||Regular||≤20 business days|
|FAST||≤15 business days|
|Testing design|| |
|Genome wide analysis of structural variants||CentoArray® (chromosomal microarray analysis, CMA)|
|Raw data||Raw data available free-of-charge for download (FASTQ, BAM, VCF files) along with filtered and annotated variant table (XLS file) for further research|
|Life-long diagnostic support|| |
*Solo: only the affected index patient is tested; Duo: index patient and affected or unaffected family member are tested; Trio: index patient and two family members, affected or unaffected are tested; PLUS: additional family member beyond Trio is tested. Mitochondrial genome analysis is performed only for the index patient and maternal samples
**More details at Variant Reclassification Program
***We do not offer WES-based CNV and mitochondrial genome analysis with CentoXome Prenatal due to technical limitation. More details about Prenatal Testing
WGS data analysis to pinpoint the disease-causing variant(s) among millions of variants remains a challenge. CentoGenome leverages our experience in analyzing tens of thousands of genomes/exomes from patients worldwide, to help you diagnose complex and unsolved cases.
When choosing CentoGenome, physicians, patients and partners can rest assured they will receive high-quality sequencing with accurate data analysis and interpretation. documented in comprehensive medical reports.
Our advanced bioinformatics pipeline and state-of-the-art artificial intelligence (AI) accurately identifies and prioritizes disease-causing variants.
Our best-in-class medical reports rest on 3 main pillars:
- Our in-depth expertise in clinical interpretation, in line with international best practice guidelines
- meticuluous curation of our multi-ethnic Bio/Databank which contains unique variant and multiomic data from over 120 countries.
- Our team of highly trained clinical geneticists and scientists interpret the data and cross-check every medical report.
Specific, detailed clinical information including family history is critical to maximise the power of WGS. Several studies have shown that the chances of having a clinically useful genetic result increases with the quality of the clinical information provided.5,20
Test reports always contain clear actionable clinical results, recommendations, and follow-up options. They are phenotype-driven and focused on reporting findings related to the patient’s clinical presentation/patient’s indications.
Integrated genomic and biochemical testing facilitates the decision on the pathogenicity of clinical variants leading to higher diagnostic yield
Biochemical testing allows for orthogonal confirmation of disease – accelerating the path to a diagnosis by avoiding stepwise testing
Multiomics provides a complete clinical picture – enabling the assessment of disease severity and thus accelerating personalized treatments
Variant Reclassification: When, Why, How
Discover how CENTOGENE’s variant reclassification enables us to provide you with the latest and highest quality data for the most up-to-date diagnosis.
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CentoGenome MOx Trio – Index, Positive Main and Secondary Findings, and with Carriership Findings
Positive Result – Pathogenic variants identified
CentoGenome MOx Trio – Mother, Carrier Status Confirmed, Negative Secondary Findings
CARRIER STATUS CONFIRMED – Pathogenic variant identified
1Lionel et al. 2018, PMID: 28771251; 2Sanghvi et al. 2018, PMID: 9144510; 3Clark et al. 2018; PMID: 30002876; 4Stavropoulos et al. 2016, PMID: 28567303; 5Bertoli-Avella et al. 2020, PMID: 32860008; 6Bick et al. 2019, PMID: 31023718; 7Cheema et al. 2020, PMID: 33083013; 8Boycott et al. 2015, PMID: 25951830; 9Chinese Medical Doctor Association Medical Genetics Branch 2019, PMID: 31216797; 10Manickam et al. 2021, PMID: 34211152; 11Sachdev et al. 2021., PMID: 33566436; 12Souche et al. 2022. PMID: 35577938; 13Kingsmore et al. 2019, PMID: 31564432; 14Petrikin et al. 2018, PMID: 29449963; 15Soden et al. 2014; PMID: 25473036; 16Van Diemen et al. 2017, PMID: 28939701; 17Willig i2015, PMID: 25937001; 18Liu i 2019, PMID: 31216405; 19Smith. et al. 2019, PMID: 29760485; 20Köhler et al. 2019, PMID: 30476213; 21Clinical Genome Resource. https://www.clinicalgenome.org/ [15/02/2022]; 22Miller et al. 2021, PMID: 34012069; 23Richards et al. 2015, PMID: 25741868