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 insufficient 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 Non-coding variants, such as intergenic and intronic pathogenic variants, are growing in number and importance, spanning from sequence variants to more complex structural variations.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 world’s largest rare disease-centric Bio/Databank from the leader and trusted partner in rare disease diagnostics
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 one of the most extensive ranges 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. 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 your patients valuable time to diagnosis 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. We particularly recommend CentoGenome for patients when:
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)
- Suspected of a microdeletion or microduplication syndrome (e.g., patients with neurodevelopmental delay, multiple dysmorphisms and/or malformations, growth delay)
- Suspected mitochondrial disease (e.g., patient with muscular weakness, cardiomyopathy, visual problems)
Prior testing did not provide a conclusive diagnosis, like:
- Patient with autosomal dominant spastic paraplegia and with a negative result for the gene panel
- Patient with neurodevelopmental delay, with similarly affected siblings, and a negative testing with microarrays and WES
- Any case with suspected genetic disease and negative WES
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 and covers a broad spectrum of disorders encompassing >7,000 rare diseases.
Tailored Services to Your Patient's Needs
We offer flexible testing options and additional services that allow you to tailor the CentoGenome analysis to you patient’s needs, as for example WGS for ongoing pregnancies with fetal abnormalities for prenatal diagnostics and expedited WGS for critically ill patients that need rapid and precise genetic diagnosis.
Committed to Improving the Lives of Patients With Rare Diseases
CentoGenome is paired with life-long diagnostic support via a free-of-charge and proactive reclassification program, as well as an affordable case-level reanalysis in case of uncertain or negative results. WGS diagnostic yield is continuously increasing due to the rapid rate of new gene-disease discoveries, and it is estimated that about 10-20% of undiagnosed patients can be diagnosed by reclassification and genomic data reanalysis.7
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).8-12 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
Options & Additional Services
|Turnaround time||Regular||≤20 business days|
|FAST||≤15 business days|
|Testing design|| |
|Prenatal testing*|| |
|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
*More details at Prenatal Testing
**More details at Variant Reclassification Program
In WGS, data analysis and identifying the disease-causing variants among millions of variants is still a challenge. We have the experience of analyzing tens of thousands of clinical genomes/exomes from patients worldwide, and with CentoGenome we can help you to diagnose complex and unsolved cases by finding the clinically important variants.
When choosing our WGS services, physicians, patients, and partners can feel confident that they will receive high-quality sequencing combined with best data analysis and interpretation, documented in comprehensive medical reports. By combining deep phenotype data with genotype data using our advanced bioinformatics pipeline and state-of-the-art artificial intelligence (AI) algorithms, we accurately identify and prioritize disease-causing variants to deliver best-in-class clinical interpretation and reporting. The quality of our medical reports is based on our clinical interpretation expertise, best-in-class curated variant data from our Bio/Databank, and international best-practice guidelines. A team of highly trained clinical geneticists and scientists interpret the data and cross-check every medical report. All historical high-quality classifications are curated and codified in our Bio/Databank, which is a reference for diagnostic decisions and classifications. This data repository covers a wide range of ethnicities, unique variant data, and multiomic data from more than 120 countries.
Our medical reports are phenotype-driven and focused on reporting findings related to the patient’s clinical presentation/patient’s indications. For the best WGS results, it is crucial to obtain specific and detailed clinical information about the patient and ideally also include further family members. Several studies have shown that the chances of having a clinically useful genetic result increases with the quality of the clinical information provided.5,14
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
A Journey to the Future – Whole Genome Sequencing for the Diagnosis of Heterogeneous Genetic Disorders
Last year CENTOGENE announced its new sequencing facility for rare hereditary disorders, which uses Illumina’s HiSeq X® sequencer. Some months after our journey started, our CSO Prof. Peter Bauer […]
Oncogenetics in the Clinical Practice
In this webinar you will learn the last insights in oncogenetics testing and how CENTOGENE gene panels can support you to assess the risk of a patient to develop an inherited cancer.
- BRCA 1/2
- Hereditary Cancer
Unmet Needs in Human Genomic Variant Interpretation
The quality and the precision of a final diagnosis do not consist solely of correct variant classification and clinical interpretation. Diagnosis begins at the preanalytical level, and all subsequent […]
- Mutation Database
Global Genotype–Phenotype Database for Rare Diseases
"The ability to discover genetic variants in a patient runs far ahead of the ability to interpret them. Databases with accurate descriptions of the causal relationship between the variants and the […]
- Mutation Database
Guidelines for Diagnostic Next-Generation Sequencing
The work was performed by a group of laboratory geneticists and bioinformaticians, and discussed with clinical geneticists, industry and patients’ representatives, and other stakeholders in the field […]
CentoGenome MOx Trio – Index, Positive Secondary and Additional Findings
CARRIER STATUS CONFIRMED – Likely pathogenic variant identified
CentoGenome MOx Trio – Mother, Carrier Status Confirmed, Negative Secondary Findings
CARRIER STATUS CONFIRMED – Likely 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; 7Kingsmore et al. 2019, PMID: 31564432; 8Petrikin et al. 2018, PMID: 29449963; 9Soden et al. 2014; PMID: 25473036; 10Van Diemen et al. 2017, PMID: 28939701; 11Willig et al. 2015, PMID: 25937001; 14Köhler et al. 2019, PMID: 30476213; 15Miller et al. 2021, PMID: 34012069; 16Richards et al. 2015, PMID: 25741868; 17Clinical Genome Resource. https://www.clinicalgenome.org/ [15/02/2022]; 18Matthijs et al. 2026, PMID: 26508566