The chip and the sequencer are not the same test. A consumer kit reads about 700,000 pre-picked DNA spots on a chip: fast, cheap, blind to anything off the list, so its BRCA report catches only three founder variants out of a thousand-plus 1. A clinical panel sequences each gene end to end and catches the rest.
Three conditions carry almost all the payoff. A BRCA1 carrier faces 72% lifetime breast-cancer risk and 44% ovarian; removing the ovaries and tubes at 35 to 45 cuts her risk of dying from anything by about 60% over a decade 2 3. In Lynch syndrome, regular colonoscopy cut colon-cancer deaths by two-thirds 4. In familial high cholesterol (1 in 250 adults), a statin begun young turns early heart disease into a normal aging curve 5.
The second win is your prescriptions. Most people eventually take a drug whose dose depends on a liver-enzyme variant they already carry: clopidogrel after a stent, an SSRI, codeine. A 12-gene panel guiding those prescriptions cut serious drug side effects by 30% across roughly 7,000 patients 6; screening HLA-B*5701 before the HIV drug abacavir cut a severe reaction from 2.7% to zero 7.
What you order depends on what you want to find out. The highest-yield first move costs nothing: write down your family history β cancers, heart attacks, ages, three generations each side. A counselor reads it in minutes and names the test.
Pre-decide before the swab. The counselor visit settles what each result will mean, so a positive BRCA1 isn't the first time you weigh what to do.
Most of the win arrives as an absence. The heart attack that didn't happen, the polyp caught at stage 0, the drug reaction that didn't show up. The result sits in your chart for life and pays off one prescription or surgery at a time.
The fine print β when to skip it, and what people get wrong
"My 23andMe already checked BRCA." It checked three variants of a thousand-plus; a negative rules out little 1. Raw-data reinterpreters run 40% false positives on retesting 8.
"No family history means no risk." Half of carriers have none 9. And testing rarely harms: Alzheimer's-risk disclosure caused only transient anxiety 10.
Time it around your insurance. GINA bans genetic discrimination in health insurance and jobs, not in life, disability, or long-term-care coverage 11. If a positive is likely, buy those policies first. Don't test children for adult-onset conditions.
The follow-through fails more than the test. A "variant of uncertain significance" shouldn't change management but drives avoidable surgery when misread as positive. A positive is half-useful until relatives get the cascade test.
- 1Finn et al. (2018). FDA Authorization of Direct-to-Consumer Genetic Testing. JAMA. link
- 2Kuchenbaecker et al. (2017). Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers. JAMA. link
- 3Domchek et al. (2010). Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA. link
- 4JΓ€rvinen et al. (2000). Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology. link
- 5Nordestgaard et al. (2013). Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease. European Heart Journal. link
- 6Swen et al. (2023). A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study (PREPARE). Lancet. link
- 7Mallal et al. (2008). HLA-B*5701 Screening for Hypersensitivity to Abacavir (PREDICT-1). New England Journal of Medicine. link
- 8Tandy-Connor et al. (2018). False-positive results released by direct-to-consumer genetic tests highlight the importance of clinical confirmation testing for appropriate patient care. Genetics in Medicine. link
- 9Manchanda et al. (2018). Cost-effectiveness of population-based BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2 mutation testing in unselected general population women. Journal of the National Cancer Institute. link
- 10Green et al. (2009). Disclosure of APOE genotype for risk of Alzheimer's disease (REVEAL Study). New England Journal of Medicine. link
- 11U.S. Congress (2008). Genetic Information Nondiscrimination Act of 2008 (Public Law 110-233). link
Related in the handbook (15)
- β The alcohol-flush gene is one clear, actionable thing a genetic test can settle.
- β APOE e4 is among the consequential, probabilistic results clinical genetic testing can hand you.
- β Ashkenazi carrier screening is a clear example of clinical genetic testing that changes decisions.
- β BRCA testing is one slice of clinical genetic testing; a panel often checks it alongside related genes.
- β If a gene panel shows Lynch syndrome, colon screening starts earlier and runs tighter β it cuts colon-cancer death by two-thirds.
- β Alpha-1 antitrypsin deficiency is an inherited cause of COPD; one test catches it, especially with early or non-smoker disease.
- β Familial hypercholesterolemia is among the high-impact variants that make a clinical gene panel worth it.
- β Inherited conditions like G6PD deficiency are the kind of high-value, act-on-it result genetic testing can give.
- β This is one of the clear, actionable results a clinical genetic panel can deliver.
- β A narrow, clinically-targeted gene test β useful only after the symptom picture points the right way.
- β A rare case where a single genetic result directly, definitively changes a drug decision.
- β This is a targeted clinical gene test β the kind that actually changes a diagnosis, not an ancestry spit kit.
- β MTHFR is the textbook case of a genetic test that sounds important and isn't β useful context for what genetic testing can and can't tell you.
- β This is the drug-metabolism slice of the bigger genetic-testing picture β narrow but occasionally life-saving.
- β Screening relatives for type 1 diabetes is family risk testing in spirit: antibodies and genes flag who to watch years early.
Genetic Testing
Spit in a tube or get a blood draw. Two short appointments if you want it done right. No ongoing effort.
For the 1 in 50 adults carrying a high-risk cancer or heart-disease variant, knowing it means surveillance and treatment that cut all-cause death by 60% or more.
$100 for a spit kit, $250β$1,000 for a clinical panel, often covered by insurance with a family history. One-time spend.
Settled science for the high-impact variants β BRCA, Lynch, familial hypercholesterolemia, and a list of drug-metabolism genes. The fine print on consumer kits is murkier.
If you're about to start a drug like clopidogrel, an SSRI, codeine, or a chemo, a pharmacogenomic panel can flag the ones your liver handles badly before the side effects do.
For most people, a negative test is calm reassurance; for a positive, the agency of acting often offsets the initial shock. Studies find no lasting distress on average.