Clinical exome sequencing is a powerful test that can be used to help identify the cause of health and developmental problems. In many cases, an exome is used to seek answers for patients where other testing has failed to find a cause of their health problems.

Our whole exome sequencing service uses the patient’s clinical presentation (phenotype) as the basis for finding disease causing genetic variants (a phenotype driven approach). We also employ a multidisciplinary team to provide the best testing, interpretation and support services to patients and their health care providers.

What is this test?

Exome refers to specific parts of DNA that code for proteins. The exome is about 1-2% of our genome – which is the entire set or our DNA.

Whole exome sequencing aims to identify any changes or ‘variants’ in the DNA that may be responsible for genetic conditions. The number of variants in a person’s exome is large (thousands). However, most variants do not cause health problems. The challenge for health professionals is to know which variants affect health and which do not. This is why we use a multidisciplinary team of geneticists, scientists and genetic counsellors to determine the significance of any variants found during exome sequencing.

What conditions does this test look for?

Clinical exome sequencing is used to investigate complex health and developmental problems with a suspected genetic cause. It’s often used by specialist groups, such as geneticists and neurologists, to investigate specific causes of well-known, but poorly understood conditions (like intellectual disability or brain malformations).

Exome technology is also being used to identify many genetic conditions including rare syndromes, cardiac, neurological, and mitochondrial disorders.

Genetic changes identified by exome sequencing may fall into one of four categories. Testing might identify:

  • No genetic variants of significance
  • Benign variants that are unlikely to cause genetic conditions
  • Pathogenic variants that are known to cause specific genetic conditions
  • Variants of unknown significance, which lack evidence to support their nature as benign or pathogenic. Further family testing is often required to determine the clinical significance of these findings.

Clinical Exomes

Clinical exome analysis is used to investigate any complex health and developmental problem. A Medicare rebate is available in some cases.

Alport Syndrome is a genetic disorder which involves progressive loss of kidney function and may lead to severe hearing damage and eye abnormalities. This kidney related condition is caused by gene changes that significantly affect collagen in renal structures that play a vital role in filtering waste products from blood to create urine.

View Test & Specification requirements

Clinical exome sequencing is used to investigate complex health and developmental problems. It’s often used by specialist groups, such as geneticists and neurologists, to investigate specific causes of well-known, but poorly understood conditions (like intellectual disability or brain malformations).

View Test & Specification requirements

Familial hypercholesterolaemia (FH) is a common, hereditary, autosomal dominant condition causing high cholesterol.

View Test & Specification requirements
How do I arrange a test?

VCGS offers comprehensive exome testing in addition to some bulk billed exome testing.

Testing covered by Medicare

A Medicare item number exists for some exome testing:

  • For Alport syndrome. Testing must be requested by a clinical geneticist or specialist nephrologist and meet the eligibility criteria.
  • For childhood syndromes and intellectual disability. Testing must be requested by a clinical geneticist or paediatrician and meet the Medicare eligibility criteria.

The bulk billed exome for childhood syndromes and ID differs from our comprehensive exome in that:

  • Gene Panels must be selected from the phenotype specific, pre-curated panels available on the PanelApp Australia website. Custom gene panels are not accepted.
  • Analysis will be focused on variants that match the expected inheritance patterns.
  • Additional requests to search for unrelated conditions or carrier status, and upgrade options such as rapid turnaround time, are not available.
  • Standard turnaround time of up 9 months.

Comprehensive exome service

Our comprehensive service offers greater flexibility in testing, including custom gene panels and a quicker turnaround time of 3-4 months. However, it cannot be bulk billed. A Medicare rebate can be claimed following payment for the test in full.

For all exome testing, discussion with our clinical exome team is required. A test request form and completed patient consent is also required.

Please contact our team for more information about exome testing.

P: 1300 118 247
E: [email protected]

Frequently asked questions

Exactly how does exome sequencing work?

To understand sequencing, it’s helpful to understand some basic biology.

The cell is the basic building block of all living things. Humans have billions of cells that contain the genetic information for how the body develops, grows and functions.

This genetic information is stored in DNA. The DNA is ‘housed’ in structures called the chromosomes. DNA is made of four chemicals or bases, represented by the letters A, T, C and G (adenine, thymine, cytosine and guanine). These bases form a unique sequence and changes (or variants) to this sequence can cause disease. A person's entire genetic sequence is known as their genome.

Certain parts of the genome are called genes. Humans have around 23,000 genes and they all play a different role in the body (such as determining eye colour or how we break down certain drugs). It can be useful to think of the genome as a book, where each of the chapters represents a chromosome. Sentences in these chapters would be the genes and the letters that make up each word can be considered the DNA bases. In the case of humans, the book has over 3.2 billion letters.

Exome sequencing is a process that ‘reads’ the particular part of genes that are thought to be most important for health. These parts are called exons. These ‘reads’ contain large amounts of genetic sequence information, which would require hundreds of hours for a scientist to analyse manually. Computers are used to quickly identify variants in the genetic information.

This list of variants is then ‘interpreted’ by comparing the results with databases that list variants known or suspected of being associated with genetic conditions. Interpretation is the most complicated and time-consuming component of exome sequencing because it involves input from many health professionals from different specialties to determine the significance of each variant detected.

How much does a clinical exome cost?

Please contact the laboratory for current pricing.
A Medicare rebate may be available for some patients who meet strict eligibility criteria.

What do my results mean?

Once your sample has been tested, a team of experts review any DNA changes or variants found. The team will determine the significance of any variants, using all the available published scientific literature.

Variants fall into a number of categories:

Class 5: Pathogenic Variant:

Pathogenic variants are considered disease-causing

  • At-risk unaffected relatives can be offered predictive gene testing.
  • Other affected relatives can be offered confirmatory testing.
  • Prenatal diagnosis for the pathogenic variant is possible.

Class 4: Likely pathogenic variant:

The level of evidence that likely pathogenic variants are disease-causing is very high.

  • At-risk unaffected relatives can be offered gene testing in conjunction with clinical screening.
  • Other affected relatives can be offered confirmatory testing.
  • The variant may be considered for use in prenatal diagnosis after detailed discussion with a clinical geneticist or genetic counsellor.

Class 3A: Variant(s) of unknown significance with high clinical significance:

VUS with high clinical significance are variants that have evidence to suggest they are pathogenic but there is not enough information to classify them as class 4.

  • Class 3A variants cannot be used for predictive testing or prenatal diagnosis.
  • Co-segregation studies in affected relatives, or testing to determine if the variant is de-novo is strongly recommended as these studies may provide additional evidence to clarify the pathogenicity of class 3A variants.
  • These variants may be re-classified based on new information; for example, family and/or functional studies (if performed).

Class 3B: Variant(s) of unknown significance:

Class 3B VUS are variants for which there is insufficient evidence to classify the variant as either disease causing or likely benign.

  • Class 3B variants cannot be used for predictive testing or prenatal diagnosis.
  • In selected families, co-segregation studies in affected relatives may help to clarify pathogenicity of a class 3 VUS.

Class 3C: Variant(s) of unknown significance with low clinical significance:

Class 3C VUS are variant(s) for which the evidence suggests they are likely to be benign.

  • Class 3C variants cannot be used for predictive testing or prenatal diagnosis.
No variant of significance was found.
  • Reanalysis options may be considered if the family history strongly indicates a genetic cause.

In some cases, patients might receive an ‘incidental finding’. An incidental or secondary finding is one that is not related to your condition and may have been found by chance. To minimise incidental findings, the laboratory specifically excludes sequencing certain genes known to cause adult-onset cancer, cardiac and neurological conditions. Your doctor will discuss any incidental findings with you and refer if necessary.

What happens to my genetic information?

Clinical Exome sequencing generates a large amount of genetic information. Access to and storage of genetic information is strictly governed by national laboratory and health privacy guidelines. You will be required to sign a consent form for exome sequencing which will describe how your information can be used.