Whole Exome Sequencing – Getchecked Clinic
It takes approx. 7 years to diagnose a patient with a rare disease. With Getchecked Whole Exome Sequencing, we can turn those years into days – powered by our best-in-class insights based on superior technology, our extensive clinical experience, and wealth of genetic data in rare diseases.
Getchecked’s Enhanced Whole Exome Sequencing Service
Overcoming the Obstacles of Rare Disease Diagnostics with Getchecked Clinic
With more than 7,000 identified rare diseases and approximately 80% being linked to genetic causes, diagnosing rare disease patients can often be difficult – resulting in lengthy, expensive, and emotional diagnostic odysseys.1,2
With WES, this doesn’t have to be the case. Containing the majority (~85%) of known disease-causing changes, WES uncovers the cause of rare diseases in less time and at a lower overall cost – leading to better patient outcomes. With Getchecked Clinic, we’ve taken WES to the next level. Enhanced to provide unparallel clinical coverage and diagnostic power in a single test, our product design and medical interpretation utilizes the world’s largest rare disease-centric Bio/Databank containing >31 million unique variants from over 120 countries.
The Results: Diagnosing complex and unsolved patient cases – quicker and with the highest levels of certainty.
Why Choose Getchecked WES?
Best-in-class insights from the leader & trusted partner in rare disease diagnostics – Turn Our Expertise Into Your Advantage
Superior technology from the experts in omics testing for rare diseases – Turn Your Open Questions Into Answers
Life-long support by a team dedicated to improving the lives of patients with rare diseases – Turn Our Commitment Into Your Promise
Superior Technology With Unmatched Clinical Coverage and Diagnostic Power in a Single Test
GetcheckedXome’s design and service delivers the ideal quality and performance from the world leader and trusted partner in rare disease diagnostics, with outstanding clinical coverage and unmatched clinical diagnostic power in a single test. Coupling insights from our extensive and unique rare disease-centric Bio/Databank with superior omics technology, patients and physicians benefit from a unique approach that increases diagnostic yield by up to 20% compared to routine WES3-12 via enhanced coverage of the exome, full mitochondrial genome, and known clinically-associated genes and variants.
Features & Performance
- Mean depth ≥100 x
- Highly uniform coverage of the entire exome (~20,000 genes), +/- 10 bp exon-intron boundaries, and complete mitochondrial genome (37 genes); with ≥ 98.0% target regions covered at ≥20 x
- 8,000 disease-associated genes (OMIM®, HGMD®, Getchecked Clinic's rare disease-centric Bio/Databank), with ≥99.0% target regions covered at ≥20 x
- >99.0% of all known clinically relevant variants in coding and non-coding regions (HGMD®, ClinVar, Getchecked Clinic's rare disease-centric Bio/Databank)
- Highly sensitive and specific detection of SNVs, InDels, CNVs of exon-level to cytogenomic-level changes, UPD*, and mtDNA variants with heteroplasmy ≥15%
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Sensitivity
SNVs and InDels (≤55 bp) >99.6%
CNVs (≥3 exons)** >95.0% - Specificity of >99.9% is guaranteed for all reported variants**
SNVs: single nucleotide variants; InDels: small insertions/deletions; CNVs: copy number variations; UPD: uniparental disomy; mtDNA: mitochondrial DNA
*UPD screening is performed using an in-house specific algorithm for the following well-known clinically relevant chromosomal regions: 6q24, 7, 11p15.5, 14q32, 15q11q13, 20q13 and 20
**CNV detection software has a sensitivity >95.0% for all homozygous/hemizygous and mitochondrial deletions, as well as heterozygous deletions/duplications and homozygous/hemizygous duplications spanning at least three consecutive exons
***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, MLPA; quantitative polymerase chain reaction, qPCR; or chromosomal microarray, CMA)
When Is WES Recommended?
We recommend WES for complex and undiagnosed cases with suspicion of genetic causes.
WES is conventionally recommended when patients present complex, heterogeneous phenotypes that are suggestive of multiple conditions or are otherwise unclear or atypical. WES may also be recommended when a prior genetic test was unsuccessful. The latest clinical evidence also supports WES as a first-line test when a patient’s symptoms or family history suggests a genetic cause of the diseases. This is especially true for neurodevelopmental disorders, including intellectual disability, global developmental delay, and autism spectrum disorder due to the high diagnostic yield.10, 13 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.14 The test results from WES 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.10, 14–17
We particularly recommend Getchecked Clinic's for patients when:
- Symptoms are very broad, complex, or unspecific, not pointing towards specific disease or typical phenotype e.g., patients with developmental delay, intellectual disability, autism spectrum disorder, epilepsy
- Suspicion of chromosomal imbalances, microdeletion, or microduplication syndromes e.g., children with global development delay, and/or multiple congenital anomalies, DiGeorge syndrome
- Clinical suspicion of mitochondrial disease e.g., patients with muscular weakness, cardiomyopathy, visual problems
- A severe presentation in the neonatal or childhood period e.g., neonate babies and infants critically ill in Neonatal and Pediatric Intensive Care Units (NICU and PICU, respectively)
- Prior genetic testing did not provide a conclusive diagnosis e.g., patient with neurodevelopmental delay, with similarly affected siblings, and negative testing with microarrays
- Need a cost-conscious alternative to Whole Genome Sequencing (WGS)
GetcheckedXome can help 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 Paired With Life-Long Support
We offer flexible testing options and additional services to provide a Getchecked Clinic’s analysis tailored to patients’ needs, including WES for ongoing pregnancies with fetal abnormalities for prenatal diagnostics (Getchecked Clinic Prenatal). Additionally, we offer an advanced multiomic WES solution, Getchecked Clinic MOx, which integrates deep exomic and biochemical insights in a single test to enable early diagnosis, better prognosis, and optimized treatment planning.
Committed to improving the lives of patients with rare diseases, GetcheckedXome 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. WES 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.15, 18
Options & Additional Services
Turnaround time
Fast: ≤15 business days
Testing design
Chromosomal Microarry Analysis, (CMA)
- Proactive variant-level reclassification at no extra cost**
- Case-level reanalysis at an affordable cost in case of uncertain or negative results
- Expedited and prioritized testing (≤ 15 business days) specifically designed for ongoing pregnancies***
- Includes cell culture and maternal contamination testing
GetcheckedXome MOx
- ntegrates WES with biochemical testing for inherited metabolic disorders (IMDs) and hereditary angioedema (HAE), including proprietary biomarkers, in a single solution
- Biochemical testing allows for orthogonal confirmation of disease accelerating the diagnosis path by avoiding stepwise testing
- Indicated for patients with complex and overlapping symptoms, varying age of onset and severity, or symptoms suggestive of IMDs or HAE (e.g., babies and children critically ill that need a fast diagnosis, babies with abnormal newborn screening results, patients with symptoms related to neurological conditions of unknown etiology)
*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 Getchecked Clinic’s Prenatal due to technical limitation. More details about Prenatal Testing
Best-in-Class Insights by the Leader & Trusted Partner in Rare Disease Diagnostics
When choosing our WES, 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 artificial intelligence (AI), we accurately identify and prioritize disease-causing variants to deliver best-in-class clinical interpretation and reporting.
GetcheckedXome always includes medical reporting 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 rare-disease centric 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.
Why Choose GetcheckedXOME?
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
