The majority of rare genetic diseases are caused by a variant within a gene. However, it's difficult to pinpoint one gene or disease, based on clinical symptoms. This is due to similarities between symptoms which may or may not be the result of disease-causing variants.
To maximize diagnostic yield, we utilize whole exome sequencing, a technology which interprets >99% of the protein-coding regions within the human genome. The human genome contains 20,000+ genes, and the protein coding region makes up around 1-2% of the human genome.
Why is decoding all genes required? Genetic defects in different genes could lead to common symptoms.
For example, if a patient has symptoms related to nervous system, 3,394 diseases with different genetic origins could be the cause.
Therefore, all 3,394 diseases need to be tested for diagnosis. To test all rare genetic diseases to maximize diagnostic yield, we decode all genes.
*Our test is not clinically validated for copy number variants; thus, these findings should be validated by an alternate clinical test that is designed to identify such variants.
100,000+ genetic variants may be identified with each patient. Each variant needs to be interpreted for its association with the patient’s symptoms.
Each of these variants are interpreted following the ACMG Standards and Guidelines (Richards S et al., 2015). Each variant, which per guidelines must be interpreted by numerous perspectives and data constraints, takes ~90 minutes to interpret by a medical geneticist.
Here at 3billion, we’ve automated this process entirely, via our variant interpretation system—EVIDENCE—which has advantages when compared to human experts:
Using WES-based tests, rare disease patients receive diagnoses at a rate of 25~57.5% (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.
Due to additional costs which are associated with interpretation during reanalysis, undiagnosed patients are faced with a financial burden. This is a large obstacle which we sympathize with.
EVIDENCE makes daily reanalysis possible. By reducing both time and cost to interpret a patient’s genome for newly-discovered rare diseases, the overall process is substantially more efficient.
At 3billion, we understand how difficult affordability may be for such services. That’s why we provide free reanalysis for patients who fail to receive diagnosis, from the initial trial until they are successfully diagnosed and end their diagnostic odyssey.
3billion is accredited by the Korean Center for Disease Control (KCDC) as a genetic testing provider, and is currently in the process of obtaining CAP certification.
We've collaborated with 120+ medical institutions spanning across 40+ countries, which have used our test to diagnose 10,000+ rare disease patients. In our initial validation study (N=330), ~43% of patients received definite diagnoses after clinical reassessment and family segregation testing (Seo GH et al., 2020).
3billion provides a list of variants identified, which may relate to a patient’s etiology. For each variant identified, the class, detailed information, and associated disease lists are provided.
Provided also are secondary findings via ACMG’s recommended list variants identified within 73 specific genes.
Our results also include further information about the test, genome sequencing coverage, depth, and limitations encountered.
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Prepare the patient’s DNA sample(s) utilizing the buccal swab, EDTA test, or DBS test. The sampling kid is provided upon customer request. If you prefer to use your own sampling kit, please refer to the sample preparation guideline, found here.
Send the patient’s samples, included with the printed order information page, which is provided during the ordering process. Sample transportation is handled by a trusted global courier service.
We receive the sample at 3billion, and genome sequencing is conducted on the sample within our lab by medical geneticists.
Diagnostic grade variants are independently confirmed by Sanger validation. The final result(s) is/are delivered to the physician.