The average human has a total of 20,000-25,000 genes in their body. With so many genes in our DNA, it’s difficult to believe that a defect in one of them can determine the entire course of an individual’s life, yet that is the unfortunate reality of chronic illness patients.
In April, I shared a survey hosted by Probably Genetic—a company that performs patient-initiated whole-exome sequencing (WES) to uncover underlying genetic conditions.
Read Probably Genetic Survey: Find the Cause of Your Chronic Illness.
Since then, I’ve had the opportunity to receive a genetic sequencing kit myself, send in my sample for whole-exome sequencing (WES), and discuss my results with the clinician network.
The Process
To begin, I filled out the intake survey offered online. After completing the survey about my medical history and past experience with genetic testing, Probably Genetic mailed out my testing kit. The box on my doorstep included a test tube, a preservation solution, and a biohazard bag. While genetic testing is complex, Probably Genetic outlines the directions so that anybody can follow them with ease. Clear instructions are depicted on the lid of the inside of the box.
Watch Finding the Cause of Chronic Illness | Probably Genetic Whole Exome Sequencing Unboxing.
Step 1: Prepare Your Sample
Do not brush your teeth, smoke, or eat 30-minutes prior to collecting your sample. Remove lip makeup and rinse your mouth. I collected my sample shortly after waking in the morning to ensure it was concentrated enough for an accurate test.
During my collection, I struggled with having enough saliva. Stimulating the salivary glands by making a fist and rolling them over the cheeks in circular motions encourages saliva production more.
Step 2: Collect Your Sample
Place the tube near your mouth. Spit saliva up to the red line marked on the test tube. Exclude bubbles.
My collection was extremely foamy with bubbles. Even when bubbles exceed the line, that does not matter. You still have to continue to spit into the tube until clear saliva is up to the red line.
Step 3: Preserve Your Sample
Remove the blue preservation solution from the box. Squeeze the bottle into the test tube until it is empty. Close the lid to the test tube and rock the sample back and forth to mix evenly.
Step 4: Mailing The Box
Put the sample into the biohazard bag, then place the bag into the original sample box. Remove the tape strip to seal it. The sample is shipped back in the same box it was delivered in. Postage is prepaid.
Step 5: Register The Kit
Before you are given your results, you must register the kit online through the website. Expect an email informing you that the company has received your sample.
Step 6: Results – Consult With a Genetic Counselor
In about 6 to 8 weeks, you will be sent an email notification stating the results are in. The email includes a link to schedule a date and time for a 30-minute consultation with a genetic counselor. The group of genetic counselors works closely with Probably Genetic. Patients are given the option to have the genetic counseling appointment via telephone or telehealth video. I opted for the telehealth video appointment to discuss my results with the Genetic Counseling Team at PWNHealth.
Discussing My Results
Once my genetic results were back, I received a PDF copy of my report via email.
I had previously had whole-exome sequencing through my geneticist, so it was interesting to be able to compare the findings. My first experience with sequencing identified multiple genetic mutations:
- KCNQ1: a known pathogenic variant associated with long QT syndrome, arrhythmias, and sudden cardiac arrest
- FLNC: a variant of uncertain significance affecting the filamin- 2 protein expressed in cardiac and skeletal muscle; related to myopathies
- TTC7A: a variant of uncertain significance connected to early-onset inflammatory bowel disease, immune deficiency, and intestinal atresias and obstructions; my mutations are compound heterozygous. After sending my report to the researcher, he confirmed my variants are disease-causing.
- MEFV: a variant of uncertain significance that causes Familial Mediterranean Fever in some cases
*A variant of uncertain significance is a mutation in which the effects of that mutation on the patient is unknown. There is not sufficient research to confirm or deny a causative disease. 75% of the time, these variants are found to be benign.
I was not surprised that the genetic counselor with PWNHealth was prepared to discuss my pathogenic KCNQ1 mutation. He was very thorough in explaining what that gene does, along with the consequences of harboring such a mutation. He elaborated on possible treatments and inquired about my family’s health history, stressing the importance of informing other family members to have cardiac evaluations because they likely have the mutation.
At the end of the consult, I was asked if I had any questions and offered information to join a study at the NIH for families with genetic cardiac conditions. Within a day or two of the consult, I received an email with a consult report consisting of the analysis, family letter, and a summary of what the genetic counselor and I discussed. Overall, the process went smoothly! Had I not already been aware of my genetic condition, I still would have been content with the information shared during my consult.
The Pros and Cons of Probably Genetic Whole Exome Sequencing
Pros
- Probably Genetic is more accessible to patients. Some patients are unable to have WES testing ordered through their home team of physicians due to a lack of care. Probably Genetic bypasses that issue.
- Whole-exome sequencing (WES) is less costly through Probably Genetic than paying out of pocket for the testing if it is not covered by insurance when ordered through the patient’s home team.
- Probably Genetic has physicians available to determine the necessity of WES testing, as well as to clarify any questions regarding the process.
- Results are discussed with an actual genetic counselor. Patients are not left alone to interpret results.
Cons
- Variants of uncertain significance are not reported to the patient. I was confused as to why my FLNC, MEFV, and TTC7A mutations were not mentioned during the consult or on the genetic report. It was later explained to me that Probably Genetic does pick up on variants of uncertain significance, and Probably Genetic is aware, but they are not revealed to patients. This is a problem for cases like mine in which the mutations cause such a rare disorder (with less than 100 cases in the world) with very little research and not enough cases to confirm what is currently known. ***Probably Genetic does inform patients of variants of uncertain significance if and/or when research becomes available proving otherwise.
- Although cheaper and more accessible than the alternatives, WES testing through Probably Genetic is still out of many patients’ means.
- The intake survey does not cover an extensive symptom list.
Is Whole-Exome Sequencing Worth It?
For chronic illness patients searching for the underlying cause of their symptoms, whole-exome sequencing (WES) is well worth the investment. While it is not a guarantee the test will uncover a mutation, it does have the potential to provide life-saving information for patients and their families. Had I not had genetic testing, the KCNQ1 mutation would not have been found. Now that we are aware, my medical team is treating the condition to improve my quality of life and lessen my chances of sudden cardiac arrest. Additionally, it has lent considerable insight into my gastrointestinal symptoms that did not fit with “just” Ehlers Danlos Syndrome.
Visit probablygenetic.com to begin the WES testing process.
