New online tool to find variants that cause inherited heart disease launched by Imperial College and the Royal Brompton Hospital.

The Cardiovascular Genetics & Genomics (CGG) team at Imperial College and the Royal Brompton Hospital have launched a new online tool to interpret genetic data and find variants that cause inherited heart disease. CardioClassifier draws on expert gene-specific knowledge to produce fast and high-quality results for diagnosing inherited heart problems.

Inherited cardiac conditions affect more than 600,000 people in the UK. By understanding the genetic basis of these diseases we can better treat the patients, and also their family members who may also have inherited the condition. Genetic testing is expanding in healthcare, including the NHS, and laboratories are generating an enormous amount of data. The key challenge we now face is to sift through this huge volume of data and make sense of it.  Everyone carries hundreds of rare variants (“mutations”) in their genome – the challenge is to sort those that are important from those that are not. The hope is that by streamlining this process we can get results faster and ultimately help more patients. The Cardiovascular Genetics & Genomics team have been developing tools to improve the translation of genetic information to clinical practice, including tools to sequence important heart genes (the TruSight CardioSequencing Kit), and to interpret the sequence data. This work has been supported by the Wellcome Trust, Department of Health, the Medical Research Council, and  the British Heart Foundation.

The CCG team have built a new tool called CardioClassifier (www.cardioclassifier.org) to improve and standardise the interpretation of sequencing variants identified in patients with inherited cardiac conditions. The tool uses expert disease specific knowledge to automatically annotate (or label) the genetic variants. It is presented as an interactive website allowing users to incorporate their own data with the automated findings, to generate an integrated definitive result. The CardioClassifier’s specialised focus on cardiovascular conditions allows it to perform ahead of existing generic tools that are not so finely-tuned. There is currently no other cardiac or disease focused tool available.

How does the tool work?

• The user uploads a list of genetic variants, and selects a disease of interest
• CardioClassifier determines whether each variant impacts a gene involved in that disease
• Each variant is automatically annotated with evidence needed to ascertain its importance according to international American College of Medical Genetics and Genomics (ACMG) guidelines
• CardioClassifier returns a preliminary assessment of the variant along with all of the evidence linking it to disease
• The results are displayed in an interactive web-page, where users can add any additional data they may have from their own patients
• CardioClassifier combines its own findings with the users data to produce a final conclusion as to whether the genetic variant is disease causing or not.

CardioClassifier has three main benefits: it gathers all of the evidence needed to evaluate each genetic variant, saving time for its users; it integrates the data in a standardised and reproducible way, in line with international guidelines; and each rule that it uses to assess variants has been expertly reviewed and optimised for every gene and condition that it tests, producing the highest quality results.

CardioClassifier is freely available for the NHS and for research. For other healthcare or commercial use (including UK private practice) please contact cardioclassifier@gmail.com.