What is Whole Exome & Whole Genome Sequencing, & Is It Right for You?
You may have heard of Whole Exome Sequencing (WES) or Whole Genome Sequencing (WGS)...They’re often described as the most comprehensive genetic tests on the market.
If I’ve learned one thing from being a genetic counselor, it’s that the most comprehensive test option isn’t always the best test option for every patient. Let’s break down what these types of testing actually look at and who they work best for.
What is Exome Sequencing?
Exome sequencing is a genetic test that essentially spellchecks the “coding region” (AKA the exome) of your DNA. We all have a lot of DNA, and only about 1–2% of it actually spells out instructions for proteins. While that may seem small, most known disease-causing genetic changes live within this region.
You can think of it like reading a book, but focusing on the main text where all the juicy stuff happens. You’re getting the most important details that help tell the story without going through every footnote.
What is Genome Sequencing?
Genome sequencing takes it one step further, as it spellchecks the entire genome. This means it looks at both the exome and all the other regions of DNA that don’t code for proteins.
Why does that matter? Because some genetic changes linked to disease are outside the coding regions in areas that help turn genes on or off, or regulate how they’re expressed. Genome sequencing can sometimes catch variants that exome sequencing might miss.
It’s like reading every word of the book… all of the footnotes, commentary, and fine print.
So, if exome and genome sequencing are so comprehensive, why aren’t they the best test for everyone?
Here’s where it gets a little tricky.
Exome and genome sequencing work best for people who have a wide range of specific symptoms or physical findings. These are cases where we need to cast a wide net across many genes to find an answer. But there are a few important caveats:
Strict reporting criteria. Labs follow guidelines designed to report only variants that are diagnostic or clearly related to the reason for testing. If a variant is uncertain or unrelated, it might not appear on your report. Also, variants that don’t relate to the reason for testing might not be reported. Reporting practices can also vary between labs.
Not all variant types are detected. Even whole exome or whole genome sequencing have technical limitations and can miss certain changes.
Limited scientific understanding. There are certain conditions (like anxiety/depression, or PCOS), where we still don’t have clear genetic answers for every case. If science hasn’t uncovered a genetic cause yet, exome or genome sequencing can’t reveal it for you either.
Because of these factors, a more targeted test is usually a better choice. For example:
If there’s a known familial variant, a single-site test can give a clear yes/no answer.
If your symptoms point strongly to one condition, a targeted gene panel may be more cost-effective and actionable.
If you’re planning a pregnancy or want to understand what genetic conditions you could pass on to a child, a carrier screening panel is usually the best option, since carrier status isn’t routinely reported on exome or genome testing.
So while exome and genome sequencing are incredibly powerful, they’re not one-size-fits-all. The best test depends on your personal and family history, clinical context, and your goals for testing.
Why Work with a Genetic Counselor?
Genetic testing isn’t just about picking the biggest or newest test, it’s about choosing the right one. Genetic counselors are trained to help you find the option that fits your unique situation. Everyone’s story is different, and your genetic testing plan should reflect that.
The bottom line is, sometimes more data isn’t better. It’s about finding the right test, for the right person, at the right time.
At Golden Genetics, we help you make informed, empowered decisions about your genetic health, blending evidence-based medical genetics with integrative and functional approaches to prevention and wellness.
Book your discovery call today to discuss which type of genetic testing may be best for you.