The consent conversation for genomic testing

The same basic principles should be covered when discussing any genomic test. This discussion should include the different potential outcomes of the test, the possibility of uncertain or unexpected results, implications for both the patient and other family members, and data governance.

It is important to record that this discussion has taken place. This may be documented in the patient’s notes, but best practice is to complete a record of discussion (RoD) form – and, for tests that involve whole genome sequencing (WGS), this is mandatory.

The possible outcomes of a genomic test should be covered during the consent conversation. It’s important to communicate to the patient/family that a genomic result is not black and white — that there are shades of grey.

In general, you should advise that there are three possible outcomes:

1. A causative result is identified

A pathogenic or likely pathogenic variant in a gene consistent with the patient’s phenotype is discovered. The clinician should always double check that the patient’s clinical presentation fits with those that are usually associated with variants in the gene that has been identified. If it doesn’t fit, the cause of that patient’s clinical presentation has not been identified. If the clinician is not familiar with the associated phenotype, the patient should be referred to a specialist clinical genetics service or a service that is knowledgeable about the phenotype.

2. No causative result is identified

No pathogenic or likely pathogenic variant has been identified that can explain the patient’s clinical presentation. It’s important to discuss with the individual or parents that this does not necessarily mean that there is not a genomic cause for their condition, but that a molecular diagnosis can’t be made in the context of current knowledge and technologies. In some cases a clinical diagnosis can still be made on the basis of a patient’s clinical features. As technology and understanding advances, it is still possible that a genomic diagnosis could be made in the future.

3. A variant of uncertain significance is identified

A variant of uncertain significance (VUS) is a genomic variant about which there is insufficient data to conclude that it is either benign or pathogenic: the laboratory is ‘sitting on the fence’. Variants of uncertain significance are not considered clinically actionable and cannot be used to alter a patient or family’s management.

In some cases the laboratory may feel that further investigation of a VUS is merited, if it might result in a more definitive classification. This is usually in the case of a so-called ‘hot VUS’, in other words one that has narrowly missed a likely pathogenic classification. If so, the laboratory will highlight this and communicate with the clinical team regarding further studies.

In some instances, variants of uncertain significance are subsequently up- or downgraded with the accrual of more population-level and diagnostic data. Note however that laboratories don’t currently have the capacity or resources to monitor the status of these variants to see if the classification changes over time; this should be discussed with patients, or parents, who should be advised to reconsult in a few years’ time in case of any update.

Though rare, the possibility of unexpected or incidental findings should be discussed with individuals, or parents, ahead of testing.

You should explain that an incidental or secondary finding describes a significant result that is unexpected and not related to the reason for testing. Examples of incidental findings include:

• A pathogenic variant identified in a gene associated with a condition unrelated to the one for which genomic testing was requested.
• Identification of misattributed family relationships (such as non-paternity).
• Carrier status for an autosomal recessive condition.

A genomic result will frequently have implications for other family members. These implications will depend on a variety of factors such as the inheritance pattern, whether a variant has arisen de novo or has been inherited from an affected parent, and the penetrance of the condition.

While it would be impractical to cover all of these eventualities in clinic ahead of testing, it is important that a clinician communicates with the individual, or parents, that there may be wider familial ramifications to genomic testing. They should also be made aware that where one or more pathogenic or likely pathogenic variant(s) are identified in a patient, cascade genomic testing may be available to their family members.

Patients should be made aware that in UK laboratories, DNA is stored by default. This means that a sample is available should further genomic testing be required in the future, without the requirement for another blood sample.

Personal data is stored on secure systems and only accessed by approved staff. All data storage is compliant with GDPR regulations.

Whilst not an essential part of the consent conversation, and not requiring documentation on a record of discussion form, you may find that patients have questions about the insurance implications of genomic testing.

Up-to-date information and advice can be found in the Code on Genetic Testing and Insurance, an agreement between the UK Government and Association of British Insurers explaining what an insurance company does and does not need to know about any genomic testing that a person may have had when you apply for insurance.

• When undertaking any genomic test, it is vital to discuss the test with the patient, parent or guardian.
• This discussion should include:
  • the different potential outcomes of the test;
  • the possibility of uncertain or unexpected results;
  • implications for both the patient and other family members; and
  • data governance.
• The discussion and the patient’s decisions should be recorded.

For clinicians

• ABI: Code on Genetic Testing and Insurance
• NHS England Genomics Education Programme (GEP): Genomics in the NHS: A Clinician’s Guide to Genomic Testing in Rare Disease
• NHS England GEP: Clinician’s guide for requesting WGS: rare disease
• NHS England GEP: Facilitating Genomic Testing (5 online courses)
• NHS England GEP: Let’s Talk About…Genomic Testing (film series)

For patients

• ABI: Code on Genetic Testing and Insurance
• NHS: Genetic and Genomic Testing