Uncertainty in Genetic Testing

Genetic Test Results are not always straightforward

Genetic variation is very common.

All of us carry different genetic alterations, most of which have no bearing on our health at all (benign variation).

Harmful alterations in genes interfere with their function - and these are the type of alterations we are checking for when we perform genetic testing.

In the majority of cases, if we identify an alteration, we are able to say with some certainty whether or not it is harmful.

However, in a small proportion of cases, we find an alteration that cannot be easily categorised as harmful or benign. These alterations are called "variants of uncertain significance".

The video here below, developed by Dr Sally Ann Lynch, University College Dublin, and Dr Terri McVeigh, provides more information about variants of uncertain significance.

There are three potential outcomes of genetic testing.

  1. A harmful genetic alteration may be identified

    In this case you will be given advice about how you can minimise your cancer risk

  2. No harmful alteration is identified

    In this case, you will be given advice regarding your future cancer risk and surveillance based on the family history

  3. A "variant of uncertain significance" is identfied

    If such an alteration is identified, further tests may be required to try to determine whether or not the alteration is related to your risk of cancer.

If you are found to have a variant of uncertain significance, it is important to discuss the implications of this result with your geneticist or genetic counsellor.

A large study recently showed that a small proportion of variants of uncertain significance could be reclassified when reviewed. The authors showed that, when the variants of uncertain significance were reclassified, the majority were reclassified as harmless variation (benign variants).

It is therefore recommended that a variant of uncertain significance be treated as “innocent until proven guilty”. In such circumstances, you will be given advice regarding your future cancer risk and surveillance based on your personal and family history, in the same way you would be if no alteration was identified.