The Importance of Copy Number Variants in Genetic Testing

Invitae just published a study that it says shows the necessity of looking for dupications and deletions when testing.

Corporations fund self-validating studies all the time, but most of them don’t end up published in a Nature journal. Today, that publisher’s Genetics in Medicine outlet posted a study by genetic testing company Invitae that is noteworthy for a few reasons.

The researchers were looking to gauge the value that genetic deletions and duplications—called copy number variants (CNV)—can add to genetic testing. CNVs might be disease-causing or disease-associated (the well-known BRCA1-variation is an example), but most testing companies do not analyze for them: They typically aren’t detectable by whole-genome chromosomal microarrays often used in disease risk testing. The researchers indicate that more could be known about CNV prevalence and implications if certain advanced next-generation sequencing techniques were more widely used.

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The new study looked to a colossal data set to learn more about the phenomenon. De-identified sequence data for more than 143,000 individuals were included in the search. They found that about 10% of patients who received a report of potential disease-causing variants had CNVs, with examples across medical specialties, accounting for 4.7% of cardiac pathogenic variants to 35% of neurologic examples.

Invitae’s head of medical affairs, Swaroop Aradhya, PhD, was the study’s senior author. He called the intragenic dataset “one of the largest available” to the medical community, and added that the study did more than just help illustrate CNV prevalence. “We were able to discern properties of CNVs that help us distinguish between those most likely to cause disease versus those that exist as natural variation in the human genome,” he said.

The company’s chief medical officer, Robert Nussbaum, MD, said that the findings suggest that “CNVs are not just clinically significant, they are a critical piece of genetic information that can and should be delivered as part of comprehensive clinical testing.”

But incorporating that measure efficiently requires next-generation sequencing platforms that are capable of simultaneously preening for CNVs alongside other sequence variants. And therein lies the sale: Invitae claims to be the first commercial lab to implement such a thing.

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