Genetic tests are now routinely used as a support along the patient diagnostic pathway. Once a genetic variant has been identified, it must be classified according to its pathogenic potential. Five classes exist (Class 1 to 5): benign, likely benign, variant of unknown significance (VUS), likely pathogenic variation, and pathogenic. So far, many variations are classified as VUS or likely pathogenic variation, which are low confidence classes. In such cases, the identification of a variation does not constitute a strong benefit for optimizing diagnosis and treatment.
When bio-informatics methods fail to classify variations in high confidence classes 1, 2, or 5, biological models are used to re-classify this genetic variation by evaluating its pathogenic potential.
Variation classification can sometimes be hard to link to the clinical context. In such cases, the pathogenic status of variations classified as 1, 2 or 5 can also be confirmed upon request.
Patient-specific genetic variations are expressed in the most relevant biological models:
Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CM)
Heterologous expression systems (HEK, CHO cells...)
Nematod (C. Elegans)
Biological models are used in combination with the most accurate approaches, including:
Electrophysiology (manual and automated path-clamp)
Fluorescence microscopy (conventional and confocal)
Calcium dynamics recording
In-vivo heart function evaluation (Zebrafish)