Whole exome vs whole genome sequencing: what’s the difference?
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Whole exome and whole genome sequencing are both ways of reading a large amount of someone’s DNA in a single test, but they differ in how much they read. Exome sequencing looks at the exome, the roughly 1% to 2% of DNA that holds the instructions for making proteins and where most known disease-causing variants are found. Genome sequencing reads almost all of a person’s DNA, including the regions between and within genes, so it can pick up some types of variant that the less expensive, faster exome sequencing misses. Both are mainly used to find the cause of a suspected genetic condition, and when they do, the result can open the way for relatives to have simpler, targeted testing.1,2
Key takeaways
- Exome sequencing reads the protein-coding part of the DNA, while genome sequencing reads almost all of it, including genes in the mitochondria.
- In children with suspected genetic conditions, both tests find a diagnosis far more often than older tests, with genome sequencing finding slightly more.
- Genome sequencing can detect some changes, such as larger rearrangements and repeat expansions, that exome sequencing can miss.
- A diagnosis from either test allows relatives to have quick, targeted family variant testing.
- These tests are designed for diagnosis, whereas carrier screening for healthy couples uses a focused panel of genes.
What are exome and genome sequencing?
Human DNA contains around three billion letters, and about 20,000 genes are interspersed along it. Each gene is made up of sections called exons, which carry the code for proteins, separated by introns, stretches that do not code for proteins but can still affect how genes work. Before these technologies, genetic testing usually examined one gene, or a small panel of genes, at a time.3
Whole exome and whole genome sequencing changed this by examining thousands of genes in one test. Exome sequencing captures only the exons, which make up a small fraction of the DNA but contain most of the changes currently known to cause disease. Genome sequencing reads the exons and almost everything else as well.1 The laboratory then uses the person’s symptoms and family history to focus its analysis on the genes most likely to be relevant, rather than reporting everything it reads.
How do the two tests compare?
Which test is more likely to find an answer?
Both tests perform far better than the older approaches they replaced. A meta-analysis that pooled studies of children with suspected genetic conditions found that genome sequencing identified a cause in about 41% of children and exome sequencing in about 36%, compared with about 10% for chromosomal microarray, a common earlier test. A result also changed medical or surgical care for about 27% of children who had genome sequencing and 17% of those who had exome sequencing.2 The authors concluded that either test should be considered a first-line option for these children.
What can genome sequencing find that exome sequencing misses?
The extra reach of genome sequencing matters in a minority of cases. Because it reads more evenly across the DNA and covers the regions between exons, it is better at detecting larger structural rearrangements, changes deep inside genes and expansions of short repeated sequences. In one large study of people with rare conditions who remained undiagnosed, about 8% of the cohort received a diagnosis that required genome sequencing, many after an earlier exome test had not found an answer.4
Why isn’t genome sequencing always used?
Genome sequencing produces far more data, which takes longer to analyse, costs more and turns up more variants whose significance is not yet clear. For many people, exome sequencing will find the same answer at a lower cost. In Australia, Medicare funds both tests for children under 11 with a suspected genetic condition who meet the criteria, but guidance for paediatricians notes that exome sequencing is the right choice for most children and is currently available without out-of-pocket costs, whereas genome sequencing can involve substantial extra costs.5 See Medicare funding for genetic testing in Australia for more on what is funded.
“The best test is the one that fits the clinical question. Exome sequencing answers that question for many families, and genome sequencing is valuable when the picture is more complex or an earlier test has come back without an answer.”
Dr Matt Edwards, Clinical Geneticist, Genotype Health
What are the benefits for families?
A diagnosis can end what is often a long search for answers. It may guide treatment, connect a family with specialists and support groups, and help them understand what to expect. The benefits also reach beyond the person tested. Once whole exome or whole genome sequencing identifies the variant responsible, relatives no longer need a broad test. Instead, they can have family variant testing, which looks only for the known variant and gives a clear answer about whether they share it. This step-by-step testing of relatives, known as cascade testing, can show which family members may benefit from earlier checks and which do not need them.6
For parents, a diagnosis in one child also clarifies the chance of the condition in future pregnancies. If both parents carry a variant for a recessive condition, for example, they can look at choices that include embryo testing alongside IVF, or tests in a future pregnancy. Brothers and sisters planning their own families may then choose carrier testing too.
What results can these tests give?
There are three main types of result. A positive result means a variant has been found that explains the person’s condition. A negative result means no explanation was found with current knowledge, although the data can often be reanalysed later as more genes and variants are understood. A variant of uncertain significance is a change whose effect is not yet clear; it is not used to make medical decisions, although testing relatives can sometimes help to clarify it.7 Our guide to understanding your genetic test report explains these terms in more detail.
Because these tests read so many genes, they can also reveal secondary findings, which are variants unrelated to the reason for testing but important for health, such as those linked to some hereditary cancers or heart conditions. International guidance lists a set of genes for which these findings may be reported, and people are usually asked before testing whether they want to receive them.7,8
How does the testing process work?
Whole exome and whole genome sequencing is usually arranged by a specialist, such as a clinical geneticist or paediatrician, after a clinical assessment. Genetic counselling before testing explains what the test can and cannot show, how secondary findings are handled and what the results could mean for the family. A sample of DNA is then collected, typically from blood or saliva, and testing the person together with both biological parents (known as trio testing) often makes the results easier to interpret.5 Results can take several weeks to a few months, depending on the laboratory and urgency.
If a variant is found, a genetic counsellor explains the result and helps work out which relatives might benefit from testing. Genotype Health offers diagnostic testing on referral from a specialist, private genetic counselling and Family Variant Testing, which can check relatives for up to ten known variants. Public genetics services, found through the directory of genetic services across Australia, can also arrange funded testing for families who qualify.9 Someone with symptoms or a strong family history is best to begin with their doctor.
How is carrier screening different?
Carrier screening serves a different purpose. Rather than searching for the cause of a condition someone already has, it checks healthy people for variants they could pass on to their children. For this job, a carefully chosen panel of well-understood genes is usually more useful than analysing the whole exome. The health conditions covered by a good carrier panel are selected because they are serious, their genetics is well understood and a result can genuinely inform decisions about having children, including the availability of treatment for affected children. This keeps results clear, and it avoids the uncertain findings that come with reading thousands of genes in someone who has no symptoms.
Genotype Health offers two options. Core Carrier Screen focuses on the three conditions that Medicare funds (cystic fibrosis, SMA and fragile X syndrome), and eligible Australians are bulk-billed for it. Lineova is broader, examining 461 genes, and offers ancestry panels that add variants more common in people of Southeast Asian, Middle Eastern and North African, or Ashkenazi Jewish background. Both use a simple cheek swab, also known as a buccal swab, collected at home. The decision to screen, and which test to choose, rests with each person, and a genetic counsellor is available to talk it through.
Thinking about having children?
Learn more about carrier screening with Genotype Health: Discover Lineova or Discover Core Carrier Screen.
Questions about a family result, or which test suits? Talk with a genetic counsellor.
Further questions about exome and genome sequencing
Is exome or genome sequencing used for healthy adults?
Not usually. In Australia these tests are mainly used to diagnose suspected genetic conditions. Healthy adults wanting to understand their inherited risk are more often offered a targeted screen, such as proactive health genetic screening.
Can old exome or genome data be looked at again?
Often, yes. As new genes and variants are understood, a laboratory may be able to reanalyse existing data, sometimes finding an answer without a new sample.
Why are parents sometimes tested at the same time as a child?
Comparing the child’s DNA with both parents’ DNA helps the laboratory tell whether a variant was inherited or is new, which makes results easier to interpret. A new variant is one that is not found in the sample from either parent.
Do relatives need exome or genome sequencing too?
Usually not. Once the family variant is known, relatives can have targeted family variant testing for that specific change.
Related reading
- Everything you need to know about genetic testing and counselling
- Family variant testing: what to do when a relative has a confirmed genetic finding
- Understanding your genetic test report: a guide to common terms
- What makes a genetic test clinical-grade?
References
- MedlinePlus Genetics. What are whole exome sequencing and whole genome sequencing? [Internet]. Bethesda (MD): National Library of Medicine; [updated 2021 Jul 28; cited 2026 Oct 8]. Available from: https://medlineplus.gov/genetics/understanding/testing/sequencing/
- Clark MM, Stark Z, Farnaes L, Tan TY, White SM, Dimmock D, et al. Meta-analysis of the diagnostic and clinical utility of genome and exome sequencing and chromosomal microarray in children with suspected genetic diseases. NPJ Genom Med. 2018;3:16. doi:10.1038/s41525-018-0053-8
- Australian Genomics Health Alliance. Genomic testing fact sheet. Version 13.1 [Internet]. Melbourne: Victorian Clinical Genetics Services; 2020 Apr [cited 2026 Oct 8]. Available from: https://www.vcgs.org.au/api/media/Genomic-testing-patient-information
- Wojcik MH, Lemire G, Berger E, Zaki MS, Wissmann M, Win W, et al. Genome sequencing for diagnosing rare diseases. N Engl J Med. 2024;390(21):1985–97. doi:10.1056/NEJMoa2314761
- Melbourne Genomics Health Alliance. Guide to funded genomic tests for paediatricians [Internet]. Melbourne: Melbourne Genomics Health Alliance; [cited 2026 Oct 8]. Available from: https://www.melbournegenomics.org.au/resources/genomic-testing-paediatricians/step-step-guide-genomic-testing
- Centers for Disease Control and Prevention. About cascade testing [Internet]. Atlanta (GA): CDC; [updated 2026 Aug 12; cited 2026 Oct 8]. Available from: https://www.cdc.gov/cascade-testing/about/index.html
- NSW Health. Genomic testing information sheet [Internet]. Sydney: NSW Health; [updated 2025 Jun 4; cited 2026 Oct 8]. Available from: https://www.health.nsw.gov.au/services/Pages/nswhealth-genomic-testing-information-sheet.aspx
- Miller DT, Lee K, Abul-Husn NS, Amendola LM, Brothers K, Chung WK, et al. ACMG SF v3.2 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2023;25(8):100866. doi:10.1016/j.gim.2023.100866
- Centre for Genetics Education. Genetic services [Internet]. Sydney: NSW Health; [cited 2026 Oct 8]. Available from: https://www.genetics.edu.au/SitePages/Genetic-Services.aspx
