Many human diseases are influenced by genetics, and scientists and doctors have attempted to understand the connection between rare mutations in a person’s genome, called genetic variants, and the likelihood of a disease outcome. Some variants can have little to no effect on a person developing a particular disease, while others can have a much larger impact and are considered disease-causing, or pathogenic.

Doctors often consider the presence of pathogenic variants when recommending patient treatments. However, whether a genetic variant is pathogenic is not easy to determine. The ability to identify genetic variants in the human genome is a recently developed technology, and many laboratories study genetic variants using different methods, meaning that conclusions vary. Additionally, because genetic variants are rare, a laboratory may not have access to enough data to confidently classify a variant as pathogenic.

The national ClinGen program was founded in an attempt to increase data sharing among clinicians and scientists and create a more accurate consensus on which variants are pathogenic. Last week, the program’s first report was published in the New England Journal of Medicine, which outlined new standards to classify pathogenic genetic variants and the resulting classification outcomes. A number of genetic variants that were interpreted differently by various groups now have new classifications based on a broader range of data, meaning that scientists and doctors can be more confident when determining patient treatments.

Despite progress, many challenges remain to determine the pathogenicity of genetic variants. Much of the human genome is still not understood, so the use of genetic information always comes with a risk of uncertainty. Clinicians, scientists, patients, and their families must always be aware that while a genetic test can show you the rare mutations in your genome, it cannot tell you with absolute certainty whether or not you will develop a disease in the future.

Managing Correspondent: Emily Low

Acknowledgments: Special thanks to contributing correspondents Michael Guo and Heather Landry, both graduate students of the Genetics Department at Harvard Medical School, for providing expert advice on human genetics and disease.

Original journal article: ClinGen — The Clinical Genome Resource

Other media coverage: Study reveals flaws in gene testing; results often conflict