Complex genetic testing case studies

Published on February 25, 2021   22 min

Other Talks in the Series: Introduction to Human Genetics and Genomics

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In this talk, I want to tell you a little bit about some complicated genetic testing cases that are really quite common, particularly in terms of interpreting variants, and how we talk to the patients about these rather complex issues.
We come across variants in genes quite a lot now, and the more genes we test the more variants we find. We wanted to make sure that the test results were interpreted in the same way in different laboratories, and were explained to the patients in the same way. It's rather alarming that sometimes some variants in genes which we're not quite certain of the importance of, may be described in different ways in different parts of the country, to different members of the same family. These are the sorts of things that the ACMG guidelines are being introduced for, and they include all sorts of ways of looking at variants in order to determine how likely they are to be pathogenic. They also include population frequency guidelines, so that if there's a particular variant in a gene which is more common than five percent in the general population, then it's unlikely to be pathogenic. (Although of course, that's not always the case.). The important outcome for us, as the clinicians in dealing with these things, is to know which variants are actionable. I mean by that, a variant means that you are at significantly increased risk or decreased risk of some disease, and therefore you need to do something about it. The other issue, of course, is how reassuring is a negative test result once you've found a variant in a family, and a relative tests negative for the variant? I'll go through a few examples which show how we've been dealing with this.