Incidental genomic findings, and deciding what you want to know

What an incidental finding is

An incidental finding is a result that answers a question nobody asked. A secondary finding is close to it, a result the laboratory looks for on purpose in genes unrelated to the reason for the test, because knowing it could change your care. UK guidance from the Joint Committee on Genomics in Medicine notes that the chance of such information depends on how broad the test is and how deeply the sequence is read [1].

A targeted test for one gene rarely produces one. A whole genome can, which is why the conversation about it comes before the sample. The same guidance lists what that conversation should cover, including that results may matter to relatives, may take longer than other tests, may be uncertain, and may be reinterpreted in future [1].

Why consent comes before the sample

Once a result exists, you cannot return to not knowing it. Consent for a genomic test therefore covers what may be found as well as the test itself. The joint guidance accepts that the many possible outcomes, now and later, make fully informed and specific consent hard to achieve, and it holds that broad consent can still be valid consent [1].

A signature on its own does not show what was agreed. The guidance treats the conversation and good notes as the evidence of consent, so the decisions you make should be written into your record in plain words [1].

What a finding means, and what it does not

Most findings change a probability. When a variant turns up in someone with no personal or family history of the condition, its predictive effect is often considerably weaker than when it is found in a family already affected [1].

Large population studies show the same pattern. Across 72,434 people in two biobanks, the mean penetrance of variants classed as pathogenic was 6.9%, so most people carrying one did not have the related disease, though the figure varied widely from gene to gene [2]. For BRCA1 and BRCA2 the mean in that study was 38% [2].

Laboratories grade each variant on a five step scale, from pathogenic through uncertain significance to benign, under shared international standards [3]. A variant of uncertain significance is neither a diagnosis nor an all clear, and it is usually best left alone while evidence gathers.

The choices you can make

Before a broad test, decide these points with a doctor or genetic counsellor and write the answers down. You can revisit them, and it is easier to do so from a clear starting point.

• Whether you want to hear about conditions that can be prevented or treated early, such as some inherited heart and cancer conditions.
• Whether you want to hear about conditions where little can be done yet.
• Whether you want carrier results, which matter for children you may have more than for your own health.
• How you would like to be told, and who you would like with you when you are.
• Which relatives a finding might concern, and whether you would want help telling them.
• Whether you would like to hear if a result is reclassified later.

Risks and limitations

The main risk is worry, and sometimes further tests or procedures after a result that would never have caused illness. Uncertain results carry most of this risk, which is why they are best explained in person by someone who can put them in context.

The classification of a gene change can be revised over time. In one laboratory’s data on 1.45 million people tested for inherited cancer risk, 7.7% of unique variants of uncertain significance were reclassified, and 91.2% of those moved down to benign or likely benign [4].

There are practical effects too. Genetic data is special category data under UK data protection law, which gives it extra protection [5]. Under the UK Code on Genetic Testing and Insurance, insurers ask for a predictive genetic result only for Huntington’s disease on life cover above £500,000 [6].

Who a broad test may not suit

A broad test may not suit you if an uncertain result would trouble you for years, or if a finding would change nothing you do. If you have symptoms now, they need a diagnosis first. If a relative already carries a known variant, a targeted test for that variant usually answers the question more cleanly.

For children, UK guidance advises that testing to predict adult illness should usually be offered only where something can be done before adulthood [1]. If a close relative died suddenly and young, or you have chest pain, fainting, palpitations or breathlessness now, see a doctor promptly, and in an emergency call 999 in the UK or the local emergency number elsewhere.

Questions to ask before you test

These questions are worth asking any provider, and the answers belong in your notes.

• Which genes will be looked at for secondary findings, and against which version of the list?
• Will uncertain variants be reported to me, and who will explain them?
• Can I change my mind later about what I want to know?
• Who else will see my result, and can my data be deleted?

How The Wellness can help

Every genome option starts with a free call with one of our doctors, who talks through your family history and what you want to know before any sample is taken. The Sentinel reads the 84 genes where a finding changes what a doctor does, with a results consultation with a doctor and a registered genetic counsellor where a finding appears. About 6 in every 100 people carry a finding in one of them.

Your sample is read in an accredited laboratory, your raw data is yours to download, and it is deleted the day you ask. Where a finding calls for a specialist, we arrange the first appointment. Our clinics are on Baker Street in Marylebone and Eccleston Street in Belgravia, with GMC registered doctors.