The Online Gene Test Finds a Dangerous Mutation.

The Online Gene Test Finds a Dangerous Mutation. it's going to rather be Wrong.

Dr. Joshua Clayton, a 29-year-old radiology resident at Baylor University Center in Dallas wanted to seek out out about his ancestry.

So he sent a sample of his saliva to 23andMe, the genetic testing company.

His report was pretty mundane — no new revelations.

on the opposite hand, he sent the profile created by 23andMe to a separate company called Promethease, which promises to undertake A more in-depth analysis of genetic mutations that cause disease.

The news wasn't good.

Dr. Clayton came to a report with a sinister red box at the very best saying he had a mutation linked to Lynch syndrome, a frightening genetic disorder that leads to potentially deadly cancers at an early age.

In an interview, Dr. Clayton said he “knew, a minimum of cursorily, those false positives were common with these tests.

” But “that didn’t change the frightened feelings or concern, because I certainly couldn’t blow it off.”

After a fortnight of panic and yet another genetic test at an organization expertly in medical diagnostics, he learned the red box result was wrong.

He simply didn’t have the mutation.

More Americans are embracing consumer genetic testing, but the Food and Drug Administration limits what major firms like 23andMe or Ancestry.com can say a couple of consumer’s health.

So many people are taking an extra step: uploading all the info created by these companies to second companies for extra analysis.

But these aren't firms certified to provide medical diagnoses, nor are they sophisticated academic centers.

Companies like Promethease warn customers to not regard their results as medical diagnoses.

Mostly, they're comparing a consumer’s data to gene variants reported being linked to disease.

But it’s not within the least clear that buyers understand how uncertain their results could even be.

There aren't any systematic studies of how often the direct-to-consumer results and third party analyses are wrong.

In one small study, Ambry Genetics — a lab certified to undertake medical testing — verified 49 samples sent in by physicians whose patients had been told that that that they had disease-causing mutations by third-party interpreters.

Ambry found that 40 percent were wrong. additionally, some genetic variations classified by second companies as threatening actually were benign.

This tiny sample doesn’t prove that the false-positive rate is 40 percent.

But patients like Dr. Clayton isn't uncommon, genetic counselors say. which they're increasingly worried about the flip side: false negatives that reassure consumers who actually should be worried.

Dr. Judy Garber, director of the Center for Cancer Genetics and Prevention at the Dana- Farber Cancer Institute in Boston said one of her patients was told by a consumer the testing company she had Li-Fraumeni syndrome, which greatly raises the danger of a number of rare cancers.

Further testing showed that the diagnosis was wrong. “It causes you to stress about the people who don’t are available,” said Dr. Garber.

“People think they're getting the same quite genetic testing as they could get from a certified clinical laboratory,” said Stephany Tandy-Connor, a genetic counselor at Ambry. “Nothing could be beyond reality .”

Even some doctors are misled by the reports, she said.

Of course, companies like Ambry have an interest in ensuring their business isn't usurped by consumer testing firms.

But it’s also true that the tactic employed by consumer companies is extremely different from those employed by certified clinical laboratories.

Consumer companies' method look for changes in tiny segments of genes, rather than examining the entire gene and checking out alterations. that's cheap but not comprehensive.

And because they are not making medical diagnoses, these companies aren't subject to the sort of internal control as certified labs, which require extensive confirmation that results are free of errors.

Compounding the matter, the second company believes databases that will contain errors — so albeit the genetic alteration found by the first company is correct, the analysis is usually wrong.

Ambry found such patients in its recent analysis.

Greg Lennon, a co-founder of Promethease, said that the company’s reports include a disclaimer saying the data is “not intended for medical or health purposes.

” Customers are warned to hunt out “an independent, clinically validated test” if they're told of a mutation and to hunt out a genetic counselor.

When errors occur, they typically derive from mistakes within the raw DNA data, said Mike

Cariaso, also a co-founder of Promethease.

23andMe offers limited medical testing — as an example, trying to seek out three of the foremost common mutations in carcinoma genes that occur mostly in Ashkenazi Jews.

But there are thousands of other alterations in those genes that the company doesn't track.

The F.D.A. has given 23andMe approval to undertake to similar testing for 10 disorders linked to

genetic mutations, but not for an outsized number of others, including Lynch syndrome, that companies like Promethease look for.

The variations in DNA in 23andMe’s data “are not for medical or diagnostic use,” said Shirley Wu, the company’s director of product science.

“The data hasn’t undergone the same quite control and validation as our variations in our health reports.” The company warns customers of this before providing their data, Dr. Wu said.

For the customer who expects validated diagnoses, it’s all slightly confusing.

Testing companies like 23andMe say they are not guilty because they create it clear that their data aren't meant to be used for medical diagnoses.

The companies that provide deeper analyses, like Promethease, say they take only raw genetic profiles created elsewhere and use publicly available data to scan for mutations that can increase disease risk.

Promethease didn’t author any of it.

“So much of what I even have seen in these D.T.C. tests are false positives and cannot be trusted,” said Dr. Robert Nussbaum, a chief medic at Invitae, a medical testing lab.

Still, he added, false negatives are even more worrisome.

Dr. Clayton learned only after weeks of agonizing that his Lynch syndrome diagnosis wasn’t really a diagnosis within the least.

“My wife which I used to be talking about having children,” he recalled.

“What do I do? do I make that decision to pass this on to them?”

And what about disability insurance? If he got cancer, he won't be able to work.

But could he even get insurance? Dr. Clayton searched online for Lynch syndrome experts and located Dr. Theodora Ross, director of the cancer genetics program at the University of Texas Southwestern Medical Center in Dallas.