Improving transparency and advancing genomic science.

Sequencing technology has been developing at such a pace, that we are struggling to keep up with it in places. There have been an overwhelming number of genetic variants identified over the past couple of decades, but interpreting that into clinically actionable information is exceptionally difficult. While translational research is busy finding out what those variants are actually responsible for, there are still some very basic issues that need to be addressed – namely standardising processes and building a common language.

ClinGen was presented in The New England Journal of Medicine this week- a program to evaluate the clinical relevance of genetic variants for use in precision medicine and research.

“We’re dealing with massive amounts of information: more than 80 million genetic variants have been discovered to date, and for most of them, we have no clear understanding of their role in human health and disease,” said Heidi Rehm, PhD, associate professor of Pathology at BWH, director of the Laboratory for Molecular Medicine at Partners HealthCare Personalized Medicine, and lead author of the paper. “As genetic sequencing becomes more common, interpreting data in a meaningful way and standardizing practices is imperative. The enormity of the situation is daunting, but the potential impact on patient care has immense implications.”

This is where ClinGen is making a difference. Without standard processes, individuals, and groups, may end up interpreting the same variant in a different way. By helping laboratories to share data, and implement the standards set by the American College of Medical Genetics and Genomics, they are solving this problem of inconsistency.

The ClinVar database currently has over 170,000 variant submissions from all around the world. When you consider how many variants have been discovered, that’s just a small fraction of what’s out there. ClinVar is a crucial part of how ClinGen are going about their mission. They have formed expert working groups to interpret the strength of the gene-disease relationships, resolve differences in the interpretation of variants clinical significance found in ClinVar, and move variants into the category of ‘expert panel reviewed’. It’s a tremendous amount of work, but significantly increases the level of confidence with which those variants can be used in a clinical decision-making situation.

“Our model works a little like Wikipedia: anyone can submit variants and interpretations to the database to rapidly enable shared resources, but that content is later curated by an expert group to standardize quality,” said Rehm.

ClinVar is publicly accessible to all. As this is open to patients, ClinGen have developed a patient portal to help involve patients in sharing their own genetic data as well. The portal also helps to connect patients with researchers, and other patients with the same condition.

There is a lot of promise to what ClinGen have set out to do, but they need your help. If you have data, get over to ClinVar and submit. The more variants are in there, the more people it can help.