The 'Fantasy World' of Incidental Findings

Are incidental findings from whole-exome and whole-genome sequencing really "incidental"?

Full-text access for registered users only. Existing users login here.
New to GenomeWeb? Register here quickly for free access.

The issue is not really

The issue is not really whether "incidental" genetic findings are of secondary medical significance (no one argues that they are), but rather how to define them helpfully. When one sequences a modest set of candidate genes of known relevance to a particular disease, it is usually unlikely that one will find some other interpretable result - one doesn't normally sequence known oncogenes when one is trying to diagnose a motor neuropathy for example. The issue is when exomes are being done, lots of medically irrelevant (to an immediate diagnosis) genes get sequenced anyway. It simply does not seem appropriate to ignore all of that flood of information, yet most of it is uninterpretable. The ACMG is trying to thread a narrow path and there are bound to be differences of opinion on many details. It makes sense to implement a set of standards like these, try them out and then re-evaluate and improve them. This is not really that different than what has already been done in cytogenetics as resolution of analysis improved from light microscopy to chromosome painting to array-based CNV analysis. A genomic SNP array to check for subtelomeric deletions can still pick up a heterozygous deletion of an oncogene, which is just as much an "incidental" finding as a point mutation from exome sequencing. So there is good precedent for this stepwise approach to release of "incidental" information. The problem is more one of jargon, "incidental" may be misunderstood to mean of secondary medical significance, whereas all that is really being implied is that the finding is not directly germane to the original purpose for the test.

Please keep in mind that the

Please keep in mind that the ACMG recommendations that were just released pertain only to clinical encounters and do not comment upon genomic research.
Robert Green