Fig. 1

The GUaRDIAN framework. Clinicians refer patients and family members to GUaRDIAN consortium following which the blood/DNA samples and complete clinical investigations are shared. The samples undergo next generation sequencing, bioinformatic analyses, and variant prediction. The predicted genetic variant is checked for segregation in the family members using capillary sequencing. If a known pathogenic variant is identified, a research report is generated and sent back to the clinician. When a putative novel variant is identified, the effect of the genetic variant is modeled in a suitable system to validate the functionality of the variant and also to understand the disease mechanism. Further, the genetic variant information derived from patient/family is made available for community-level screening