A genetic variant in a gene causes a rare genetic disease. To maximize the diagnostic yield, all DNA sequences of 20,000 genes can be decoded by whole exome sequencing.
With the advanced sequencing technology, 99.3% of gene regions are decoded on average.
Why do we decode whole genes? Genetic mutations in different genes can cause common symptoms. For example, if a patient has symptoms related to the nervous system, 3,394 diseases with different genetic origins could be the cause.
This is why all 3,394 diseases need to be tested for the diagnosis.
To test all rare genetic diseases and maximize diagnostic yield, we decode all genes.
From each patient, more than 100,000 genetic variants can be identified. Each of the variants needs to be interpreted for its association with the patient's symptoms.
Each variant is interpreted by standard interpretation guidelines such as ACMG guidelines (Richards S et al, 2015). ACMG guideline is composed of 28 rules, which means each variant needs to be interpreted in each of 28 different rules with different perspective and data. It takes an average of 90 minutes to interpret a variant by a trained medical geneticist.
We developed an automated variant interpretation system, called EVIDENCE, to interpret 100,000 variants identified in each patient according to the ACMG guideline. EVIDENCE has several advantages compared to human experts as below.
Currently, 25~57.5% of rare disease patients receive diagnoses with WES based tests (Wright CF et al, 2018 , Monies D et al, 2019 , Trujillano D et al, 2017 , Stark Z et al, 2016). More than half of the rare disease patients fail to get diagnosed with genetic testing.
About 10% of patients who fail to get diagnosed at the initial trial receive a diagnosis with regular reanalysis (Machini K et al, 2019, Costain G et al, 2018). This is why we conduct regular reanalysis to maximize the diagnostic rate.
Cost is the challenge. As reanalysis requires additional interpretation cost, patients with undiagnosed rare disease face financial burden.
EVIDENCE, our fully automated interpretation system, makes monthly reanalysis possible. It reduces the time and cost to interpret a patient’s genome on newly discovered rare diseases to a fraction.
3billion provides a free reanalysis service for patients who fail to receive diagnosis at the initial trial until diagnosed
75 clinics in 27 countries have used our test to diagnose 9,500 rare disease patients. In our initial validation study on 330 rare disease patients, 51.8% of patients received definite diagnoses after clinical reassessment and family segregation testing (Seo GH et al, 2020).
3billion is a KCDC (Korean Center for Disease Control) accredited genetic testing provider and is currently in the process of CAP certification.
List of variants identified to cause diseases of patients. For each variant, class of variant interpretation, detailed information of the variants, and associated disease are provided.
List of variants identified in 59 genes recommended by ACMG for reporting incidental findings.
Overall information on the test including genome sequencing coverage, depth, and limitations.
Prepare patients’ DNA samples in the buccal swab, EDTA blood, or dried blood spot. The sampling kit is provided upon customer request. You may also use your custom sampling kit.
The quantity and quality of the sample are important. Please refer the sample preparation guideline.
Send patients’ samples with printed order information page. The order information page is provided during the order process. Sample transportation is handled by a trusted global courier service.
Once we receive the sample, genome sequencing on the sample is conducted in our lab.
More than 100,000 genetic variants identified from the sample are interpreted by a streamlined analysis system, EVIDENCE, and confirmed by medical geneticists according to ACMG guidelines.
The diagnostic grade variants are independenlty confirmed by Sanger validation. The final result is delivered to the physician.