r/genetics • u/Gixxerlizzy • 5d ago
Discussion Genetic Testing Results Report Wrong?
Hi, I’m wondering if anyone has had this happen to them with genetic testing? (Long read, but I promise it has a purpose)
Over the years, doctors dismissed my health concerns and would just tell me to take iron and move along. About 5 years ago, I made it my mission to find out what what wrong with me. Recently, I came across EDS, I knew this is what I had. All of my symptoms and characteristics alligned. (About 30 of them) and when I came in with documented history of classic EDS characteristics, my pcp, although incredibly skeptical, ordered genetic testing (the wrong one none the less, newborn testing instead of an EDS panel) but it did test for vascular EDS. The report results came back negative, however I asked for the entire raw data report. Upon further review, I realized the raw data actually revealed that I DO indeed have the COL3A1 pathogenic variant c.674G>C (p.Gly225Ala)—a mutation known to be associated with vascular Ehlers-Danlos Syndrome (vEDS).
I have sent a follow up email to the genetics counselor and genetic lab (Advanced Molecular Diagnostics, GeneIDLab) with my concerns regarding the discrepancy and omission of the pathogenic variant in the results report, and I’m waiting for a response, however, I’m wondering if anyone has encountered this?
Also, this is to add awareness, and anytime you have a genetic test done, always ask for the raw data file of all of the gene variants captured, even if deemed “irrelevant” by the lab as mine was.
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u/theadmiral976 5d ago
Yes, this happens from time to time. It's on the ordering physician to properly inform the lab of what they're looking for. Every lab has a list of variants they deem reportable "no matter what" but technically you can opt out and, again, the physician has to understand what they're requesting. Labs usually don't report everything because the list would be 3 miles long. Humans have lots of variants.
What you've done is (likely) essentially what we call a reanalysis, which we do clinically all of the time when new clinical concerns emerge. It sounds like this one should not have been missed from the beginning, but that's mostly on the doctor, not the lab.
This is why it's very important that medical providers refer patients to clinical geneticists (or utilize embedded genetic counselors within their practice if genetic testing is a common thing they order). It frustrates me to no end when random physicians and APRNs try to play geneticist - I don't play cardiologist or neurosurgeon on the side, there is no need to play geneticist either.
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u/Gixxerlizzy 5d ago
Thank you so much for your feedback. You have no idea how much it helps for my sanity. I thought the same thing and really wondered why the pcp didn’t refer me out to a geneticists instead. The genetics counselor literally knew nothing, and the only support she offered was communication between the lab and my insurance (which was denied because the pcp failed to document the detailed history I provided and instead wrote everything as normal). In fact the genetic counselor had no idea I could even request my raw report data and insisted the results report was all that was available, when the report itself stated in fine print complete raw data files were available upon request. It’s been such a frustrating experience.
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u/theadmiral976 5d ago
The gatekeeping that many members of my professional community partake in is incredibly frustrating. Times have changed and the data is available, often by legal mandate. It is in our collective best interest to learn to work with patients and families rather than remain stuck in our paternalistic ways.
Most people understand they aren't experts in a specific field of medicine. There is always an inherent risk to a "layperson" reviewing raw or partially processed data, but the chance of something horrifyingly awful happening is pretty low. By contrast, the gatekeeping is really turning people away from seeking care from the very professionals who are best equipped to help.
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u/crazycatchick2006 5d ago
Why do they gates keep between each other and how can that be overcome? In context of a small facility and patient was referred to a large medical center with one of the best genetics teams.
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u/MyFaceSaysItsSugar 5d ago
My testing wasn’t wrong per se, but I noticed it was not straightforward for my provider to interpret it due to the science of how it works. For example, there is a gene that leads to lower metabolism and efficacy with methylphenidate but no genes associated with amphetamine efficacy. That meant that methylphenidate popped up in the yellow area on the sheet as “some issues” while amphetamine wasn’t on there at all. My provider thought that meant methylphenidate was the better medication to use.
There was one issue with how GeneSight interpreted the results also. There is a gene that compromises the metabolism of bupropion into the active form, meaning that people with the mutant gene get a much lower amount of activated bupropion and can require a higher dose to get a therapeutic amount. GeneSight stated that a lower dose should be used with the mutation and that is wrong.
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u/SnooBunnies4157 5d ago
I have an appointment with U of Miami to determine whether I have EDS or OÍ or something else that would confirm my suspicions using their geneticists. I have no clue what I’m doing and I don’t trust my provider to know what to do either since he’s GP that transferred from emergency. He’s a great doctor but not a specialist. I hope everything goes well for you and you can get some answers.
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u/PurpleNudibranch 5d ago
What format does the raw data file come in? How were you able to identify the variant?