Why Genetic Tests May Call For a Second Opinion


By Meredith Salisbury

When you get your cholesterol levels after a blood test, you may grumble about the new diet your doctor recommends or the statins you have to take–but you probably don’t wonder whether the levels were wrong. We know clinical lab results are tightly regulated, so we take their accuracy as a given. Assuming the same thing about lab results from a genetic test, however, could be a mistake.

Some medical genetic tests look only for the presence or absence of well-understood gene variants, so lab reports come back simply “positive” or “negative.” For more complicated tests, which often scan whole genes or try to find rare or novel variants, the reports are more complex too. Results are returned classifying each genetic variant based on how likely it is to cause disease (in clinical parlance, ranging from “pathogenic” and “likely pathogenic” to “likely benign” and “benign”).

Like a cholesterol report, genetic results look official and authoritative. The problem is that for such complex genetic tests, the report delivers an opinion rather than a fact. To be sure, that opinion is a highly educated, highly researched, carefully considered one; but it’s an opinion nonetheless. Since more and more of us are receiving such results, it’s worth taking a moment to understand how they are determined.

For your average medical test, a tube of blood or urine is shipped off to a clinical lab, which runs it through a series of instruments. At the end of a fairly automated pipeline, the instruments generate a result: the numbers representing your cholesterol or white blood cell count or creatinine. Those numbers go straight to the lab report. There is little human participation in the process, and not coincidentally, little room for error.

A complex genetic test–that is, one looking for more than just the presence or —> Read More