Genetic variant databases play an essential role in driving precision oncology. Well annotated databases aid in offering evidence-based classification of variants for clinical actionability - including for diagnosis, therapy guidance and prognosis (e.g. HGMD, ClinVar MarkerDB, MUSTARD etc.). However a number of genetic variants, especially from diverse populations are not well represented in such databases, limiting their utility in clinical decision making. Additionally the multiple standards and criteria utilised by diagnostic laboratories to annotate variants as Pathogenic or Benign make the problem more acute for clinical interpretation of the reports and further genetic counselling and clinical actionability.

India is unique in many aspects, with a diverse and stratified population and admixture with major populations across the world , all contributing significantly to its rich genetic diversity. The recent initiatives aimed at population-scale sequencing like IndiGen have provided a unique opportunity to understand the prevalence of genetic variants in the population.

While a number of laboratories and genetic testing services offer genetic testing/screening for BRCA1 and BRCA2 genetic variants, the lack of a uniform system followed across the laboratories for the interpretation of the pathogenicity of genetic variants has limited the clinical actionability of variants in clinical settings. Such non-standard approaches have also resulted in inter-clinician and inter-lab differences in interpretation including sometimes conflicting interpretations of genetic variants and their pathogenicity. The ACMG & AMP joint guidelines for the interpretation of pathogenicity of genetic variants is a globally followed system now in place, but due to the fact that the interpretation is time-consuming, tedious and requires careful evaluation of published evidence, it is not followed widely in India.

This programme envisages the creation of a genetic  variant compendium for BRCA1 and BRCA2 derived from clinical reports from India, which would be re-classified according to the ACMG & AMP joint guidelines and made available for clinicians for ready reference. Additionally, since newer evidence has been emerging in this area, additional advancements and consequent changes in interpretation, especially for the variants of uncertain significance (VUS) would also be updated on the resource for ready reference.

Additionally, the exhaustive compendium of variants from Indian populations would enable the establishment of genetic epidemiology of BRCA1 and BRCA2 variants in Indian populations with impact in public health endeavours enabling swift, accurate diagnosis and help in genetic counselling.

Participating in the collection
Clinical collaborators are encouraged to participate in this endeavour. Collaborators are expected to share genetic variants from clinical testing (without any personal or identifiable information of the patient) along with relevant clinical notes in a predetermined proforma. Clinicians contributing towards the endeavour would be duly credited / acknowledged depending on the contributions made to the database.