By Tomi Oyedeji-Olaniyan, 23andMe Medical Communications Associate
Editor’s note: This is the first blog in a series about 23andMe+ Total Health™ and how it can aid healthcare providers in providing patient care.
When making decisions about patient care, more information can be key to developing a care plan that supports individual patient needs. As DTC genetic testing becomes more widely accessible, patients are seeking to learn more about their genetic information and how they can use it to inform their health. This has extended into traditional healthcare with it becoming increasingly more essential for healthcare professionals to be able to understand and interpret genetic testing information. However, as technology continues to evolve, different types of genetic tests provide different levels of information about a patient’s genome. 23andMe now offers patients the opportunity to access, understand and benefit from their genetic information more comprehensively through clinician-ordered exome sequencingΔ in our most advanced product offering to date, 23andMe+ Total Health.
What is exome sequencing?
Exome sequencing is an advanced, comprehensive genetic testing method that analyzes the protein coding regions of your genome, known as the exome. The exome is where the majority of known genetic variants associated with disease risk are located. Through exome sequencing, Total Health is able to detect 200 times more disease-causing variants than our genotyping service does.* This means patients can be screened for 50,000+ hereditary disease causing variants that are related to cancer, cardiovascular, metabolic, kidney, neurological and other serious health conditions.
The information gleaned from this screening may reveal genetic predispositions for conditions that have actionable preventive measures and clinical interventions. All genes that are screened have been vetted for clinical validity and all genes considered medically actionable by the American College of Medical Genetics and Genomics (ACMG) are included. This also means that sequencing results may distinctly influence patient care plans to tackle individual concerns surrounding identified genetic variants with known identified disease risk. Offering this service demonstrates 23andMe’s commitment to transforming medical care to be more personalized and precise.
Exome Sequencing vs Genotyping
Historically, 23andMe has offered reports utilizing genotyping technology, a method that efficiently and accurately screens the genome by examining DNA variants at certain pre-identified positions. These are locations in the genome where one is more likely to exhibit a variant that is associated with disease risk**. This is akin to carefully checking the spelling of keywords by focusing on important sections where typos are more common.
Sequencing approaches this differently and instead involves reading each letter of a segment of DNA in its correct order to identify changes from what is typically expected. This ultimately provides individuals with a more complete picture of genetic variants in the sequenced region and the associated risk with known variants. This would be akin to reading every single word in the book, from cover to cover and identifying any typos.
For example, our Personal Genetic Service provides a genotyped report, the BRCA1/BRCA2 (Selected Variants) Genetic Health Risk report**, which looks at 44 different variants within the BRCA1 and BRCA2 genes that are known to be highly penetrant. Our 23andMe+ Total Health membership provides an exome sequencing report that looks for thousands of variants across the BRCA1 and BRCA2 genes, in addition to thousands of variants in many other genes associated with increased cancer risks. A 2018 study showed that when compared with previous clinical care, exome sequencing-based screening identified 5 times as many individuals with BRCA1/2 cancer-risk variants1.
While genotyping is accurate, efficient and cost effective, it does not account for all variants especially in areas of the genome where less is known. Sequencing is a more comprehensive, advanced genetic screening that can find both well-known and novel genetic variants. Both of these technologies can provide clinical value with actionable results, empowering patients to improve their health and reduce disease risk.
What does this mean for my practice?
Traditionally only available through a referral or clinical trials, 23andMe is expanding accessibility by offering exome sequencing to new and existing customers. This might also mean an increase in the number of healthcare providers who might be asked to discuss exome sequencing results. Total Health partners this information with built-in consults with clinicians who have undertaken genetics training as well as a holistic clinical analysis that patients can share with their healthcare providers.
However, it is possible you might still be asked to discuss Total Health results. Click here to learn more about Total Health, including covered conditions, and stay tuned for the release of our Total Health exome sequencing sample reports. For more information on how to discuss and interpret 23andMe reports, you can watch our genetic education videos.
*Our genotyping product detects 250 health-related variants in our Carrier Status and Genetic Health Risk reports. The Exome Sequencing reports detect 50,000+ hereditary disease-causing variants.
ΔExome Sequencing and blood testing services are available to eligible customers upon completion of the intake questionnaire that must be reviewed, approved and ordered by a third-party clinician. Exome Sequencing is analyzed by a CLIA- and CAP-accredited laboratory. Blood testing is completed by Quest Diagnostics. All telehealth services are provided in accordance with the Telehealth Terms and Consent to Telehealth.
**The 23andMe PGS test uses qualitative genotyping to detect select clinically relevant variants in the genomic DNA of adults from saliva for the purpose of reporting and interpreting genetic health risks, including the 23andMe PGS Genetic Health Risk Report for BRCA1/BRCA2 (Selected Variants). Your ethnicity may affect the relevance of each report and how your genetic health risk results are interpreted. The test is not intended to diagnose any disease and does not describe a person’s overall risk of developing any type of cancer. It is not intended to tell you anything about your current state of health, or to be used to make medical decisions, including whether or not you should take a medication, how much of a medication you should take, or determine any treatments. Warnings & Limitations: The 23andMe PGS Genetic Health Risk Report for BRCA1/BRCA2 (Selected Variants) is indicated for reporting of 44 variants in the BRCA1 and BRCA2 genes. The report describes if a person’s genetic result is associated with an increased risk of developing breast cancer and ovarian cancer and may be associated with an increased risk for prostate cancer, pancreatic cancer, and potentially other cancers. The variants included in this report do not represent the majority of the BRCA1/BRCA2 variants in people of most ethnicities. This report does not include variants in other genes linked to hereditary cancers and the absence of variants included in this report does not rule out the presence of other genetic variants that may impact cancer risk. This report is for over-the-counter use by adults over the age of 18, and provides genetic information to inform discussions with a healthcare professional. The PGS test is not a substitute for visits to a healthcare professional for recommended screenings or appropriate follow-up. Results should be confirmed by an independent genetic test prescribed by your own healthcare provider before taking any medical action. For important information and limitations regarding each genetic health risk report, visit 23andme.com/test-info.
References:
Manickam, K. et.al. Exome sequencing–based screening for brca1/2 expected pathogenic variants among adult Biobank participants. JAMA Network Open, 1(5). 2018