What can a cancer gene panel tell you, and what can it miss?

If the answer is yes, the right first step isn’t an at-home test of selected variants. It is a conversation with your clinician or a genetic counselor about clinician-ordered testing that reads each gene in full. The National Cancer Institute (NCI) generally recommends counseling first, before any test for inherited cancer risk.^[1]

The patterns that point that way include cancer at a younger age than usual, related cancers on one side of the family, and a variant already found in a relative. Who should consider genetic testing for cancer lists them with the U.S. Preventive Services Task Force’s advice, and when the clinical route is the right one turns them into a checklist.

A panel reads inherited, or germline, DNA, not a tumor. Each gene on it is one where some changes raise the chance of particular cancers, and the panel asks one question of each: do you carry any of the variants it was built to look for?

Inherited variants explain a minority of cancers, 5% to 10% by NCI’s estimate,^[1] so even a perfect panel speaks to a small but important share of cancer risk, never to all of it.

There are two broad ways to test these genes.

• Checking selected variants. The lab looks only at positions picked before your sample arrives, and reports whether you carry the selected variants there. It is like checking a book for a list of known typos. This is genotyping (how genotyping works), and it is how our genetic tests work.
• Reading whole genes. Every letter of each gene is read, usually with an extra check for missing or repeated pieces. It is like proofreading every page.

The difference matters because the variants that raise cancer risk are many, and many of them are rare. NCI notes that there are hundreds of BRCA variants that could increase cancer risk,^[1] and harmful BRCA1 and BRCA2 variants are individually very rare.^[4] A test that checks a fixed list can miss a variant that isn’t on it.

At-home or clinical testing? sets the two routes side by side, with who each suits. What follows is the evidence on what a list of selected variants misses.

Larger changes matter too. In a study of 48,456 people referred for BRCA1 and BRCA2 testing, about 1 in 10 of the harmful changes found in the higher-risk group were large rearrangements, pieces of a gene that were missing or repeated, found with a separate test.^[5]

One large study shows how hard rare variants are to catch. In 49,908 UK Biobank participants, SNP chips, a kind of genotyping used in big research studies and some consumer DNA tests, found only 34.6% of the rare harmful BRCA1 and BRCA2 variants that were really there, and only 4.2% of the ones they reported were real.^[4] Those chips differ from a targeted panel, so the numbers don’t describe our test. The lesson still applies to any test of selected variants: rare variants are hard to catch, and a finding needs confirming. How lab methods compare goes into more detail.

Much of inherited cancer risk traces back to a few well-known syndromes. The table is background. It doesn’t list what any one panel checks, and a gene’s name on a panel doesn’t mean every variant in that gene is checked.

It means the lab found a variant associated with an increased risk of certain cancers.^[1] It is a risk finding, not a diagnosis. It doesn’t mean you have cancer, and it doesn’t mean you will get it.

How much the risk rises depends on the gene. In a large study of women who carry a harmful variant, the estimated risk of breast cancer by age 80 was 72% for BRCA1 and 69% for BRCA2, and of ovarian cancer 44% and 17%.^[7] By comparison, about 13% of women in the general population develop breast cancer at some point in their lives, and about 1.1% develop ovarian cancer.^[2]

Once confirmed, a variant is family news as well as yours: blood relatives can ask about testing for that same change. After a positive BRCA result walks through confirming a finding, the options and telling family.

It means none of the variants the panel checks was found. It doesn’t mean your risk is low, and it doesn’t rule out inherited risk. Other variants in the same genes, and variants in genes the panel doesn’t include, weren’t tested. NCI puts it plainly: because some direct-to-consumer tests don’t test for every harmful change in BRCA1 and BRCA2, someone could have one that the test doesn’t detect.^[2]

NCI also gives an example of how much a narrow list can miss. As of January 2024, the only direct-to-consumer test for inherited cancer risk that the FDA had authorized checked three BRCA variants, and about 80% of cancer-causing BRCA variants are missed that way.^[1] Any test of selected variants, ours included, has the same kind of limit: it can only find what is on its list.

If cancer runs in your family, a negative result settles even less. CDC says that if no variant has been found in anyone else in your family, you are still at higher risk for the cancers that run in your family.^[3] And since inherited variants explain only a minority of cancers, a clean panel never replaces the screening your clinician advises.

GeneCancer is our panel of selected variants, for people without a personal or family history of cancer. It genotypes chosen positions across 108 genes, BRCA1 and BRCA2 among them, and everything above applies to it: it reads positions, not whole genes, so a full-gene test could find variants it can’t, and a result with none found doesn’t rule out inherited risk.

• Whether you have cancer now. A panel reads inherited risk, not disease; symptoms need your doctor, whatever a report says.
• Whether you carry a variant that isn’t on the panel. A test of selected variants can’t find what it doesn’t look for, including many rare variants and larger missing or repeated pieces of a gene.^[5]
• That your risk is low. A result with no variant found doesn’t rule out inherited risk, and most cancer isn’t inherited anyway.^[1]
• What to do next. Screening plans, medicines and surgery are decided with your clinician, and only on a confirmed finding.

Looking for a genetic counselor? The National Society of Genetic Counselors keeps a public directory of counselors in the US and Canada, including ones who meet by phone or video.^[12]