The evidence underlying particular gene variants that been dubbed pathogenic is sometimes very thin, writes Ed Yong at the Atlantic. That's disconcerting, he adds, as people rely on the results of such tests to determine whether or not to have an abortion, undergo a mastectomy, or have a heart-monitoring device implanted.
For instance, Partners Healthcare's Heidi Rehm recalls a case in which her lab was asked to perform genetic testing on a fetal blood sample after an ultrasound uncovered possible evidence of Noonan syndrome. The fetus had a mutation in PTPN11, a gene that had been reported to influence Noonan syndrome risk, Yong writes. But Rehm later heard a talk from a colleague that said that the paper that indicated that that PTPN11 mutation was linked to Noonan syndrome was incorrect. Instead, that mutation is simply more common in certain ethnic groups and is not pathogenic.
"I immediately contacted the physician to find out the story with that baby," Rehm tells Yong. "And that's when I found out that the parents had terminated it."
One recent study, Yong says, found that about a quarter of mutations linked to pediatric genetic diseases have been connected based on papers with weak evidence, and even others are common variants that likely don't cause disease at all.
Researchers now are relying less on the primary literature and more on curated databases like ClinVar to gauge variants' pathogenicity, Yong says. In addition, the related ClinGen initiative is combing through disease-related genes and re-assessing them based on current knowledge and rating how strongly they are associated with disease. "They've created a measure of trust for genetic results," Yong adds.