Device description

VarSome Clinical and VarSome Pro are bioinformatics tools assisting in making diagnostic decisions or treatment strategy options, after performing genetic testing using Next-Generation Sequencing (NGS).

In the classic scenario for the use of VarSome Clinical, the process would start when a patient initially goes to visit a specialised doctor, and the doctor suspects a genetic disease based on examination of the patient. The patient would then be prescribed a genetic test for identification of pathogenic DNA variants in one or multiple candidate genes.

Consequently, as shown in Figure 1:

  1. The laboratory will take a biological sample from the patient (blood is the most common)
  2. to perform DNA extraction.
  3. This DNA is fragmented and prepared in a sequencing library.
  4. Then, hundreds of thousands, even millions of DNA fragments are sequenced using the NGS machines.
  5. A computer and specialized software is necessary to analyse the DNA reads. DNA reads must be aligned to a genome reference, the differences must be outlined and
  6. annotated with known information found in specialized databases. As the number of identified variants can easily be in the order of tens of thousands, it is still necessary to apply computer tools to classify and filter the candidate variants potentially involved in the patient disease.
  7. In a final step, a specialist must look at the results, decide which variants are reported as pathogenic and produce a diagnostic report. The diagnostic report is sent back to the doctor, who communicates the results to the patient.

The system is a secured web interface, where each user can analyse NGS data using a personal login. VarSome Clinical can analyse raw data (DNA reads) from Illumina technology (FASTQ files) or lists of already processed variants (VCF files). VarSome Pro can analyse only VCF.

VarSome Clinical automatically annotates and classifies DNA variants using a proprietary algorithm. The variants are compared with more than 33 billion reference variants that have been aggregated from a wide range of databases.

Once the variant calling and/or the variant annotation has finished, the user can access the results by a simple click in the web user interface. At this point, to filter out the irrelevant variants, the user needs to design the filters that will be applied to the variant table. Then, the pathogenic variants can be marked and exported to write the diagnostic report.

Intended Use

VarSome Clinical and VarSome Pro offers clinicians and researchers a fast and accurate solution to aid in making an informed decision and diagnosis and on the selection of the best therapies for the treatment of hereditary cancer, difficult to diagnose conditions, such as rare diseases and heterogeneous Mendelian disorders (e.g cognitive impairment, metabolic, cardiovascular, immunodeficiency diseases).

VarSome Clinical utilises variant calling pipelines for analysis of Next-Generation Sequencing data (Illumina technologies), from whole genome libraries, DNA capture-kit libraries (exome, clinical exome) and amplicon kits for germline and somatic DNA. The portal identifies and reports SNVs, indels and substitutions, as well as variant annotation to facilitate the variant curation and classification. Multi-sample analyses are also available, to perform joint-genotyping to generate a multi-sample VCF file with the merged genotypes for two or more samples. VarSome Clinical can also propose algorithmic filters for inheritance hypothesis testing.

Indication for Use

VarSome Clinical and VarSome Pro offer clinicians and researchers a solution to assist in making an informed decision and diagnosis on the selection of the best therapies for the treatment of patients of all ages for the following conditions:

  • Patients suspected to be affected by heterogeneous mendelian diseases or undiagnosed (rare) diseases.
  • Patients with common diseases that are in fact a group of rare diseases with eclectic phenotypic features, being caused by mutations in specific genes, such as developmental delay or intellectual disability, degenerative neurological diseases, immunodeficiency diseases, cardiomyopathies, etc.
  • Patients with hereditary cancer syndromes.


There are no specific contraindications associated with the VarSome Clinical, VarSome Pro or indeed NGS testing.

Warning, caution and precautions

⚠ CAUTION When using NGS to investigate the cause of a disease, clinicians and patients must be aware that the test may cover many genes, most of them unrelated to the patient disease. This would lead to discovery of secondary or incidental findings on genes causing other diseases, e.g. cancer predisposition status (Kuhlen and Borkhardt 2015). Recently, policy statements from two major regulatory agencies (AMP and ACMG) have provided a list of recommendations (Green et al. 2013; Allyse and Michie 2013; ACMG Board of Directors 2015; Hegde et al. 2015). However, each country has its own directives about incidental finding reporting. Therefore, it is extremely important that the patient, or their legal representative, is informed of the incurred risks and that the patient’s decision is recorded in an “informed consent” document (Anderson et al. 2016). It is the responsibility of the treating clinician to collect the informed consent form before ordering any NGS test, and ensure that patient understands the potential outcomes of the test.