The shift from genetic testing of individual genes to exome and genome sequencing has been accompanied by new challenges in genome interpretation. The American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) have published Standards and Guidelines for the Interpretation of Sequence Variants. To enable wide application of the ACMG/AMP and similar guidelines and the development of collective knowledge by the community, ClinGen has developed the ClinGen Pathogenicity Calculator. By automating the formal reasoning, the Calculator eliminates errors in rule application and makes it possible to automatically calculate provisional conclusions based on latest evidence. Moreover, the Calculator makes reasoning explicit by documenting applicable rules, evidence codes, and links to supporting data. By explicitly communicating the reasoning behind a conclusion about pathogenicity of any specific variant, the Calculator enables critical evaluation of the reasoning and facilitates resolution of conflicting conclusions. Using the current Calculator interface one may (1) identify an allele within the ClinGen Allele Registry; (2) register a new allele if not present in the Registry; (3) enter ACMG/AMP-style evidence tags and links to supporting data for each tag; (4) generate guideline-based conclusions from the evidence tags; (5) permanently store and share reasoning behind each conclusion within a collaborating group; (6) generate variant reports printable as PDF and URL links for public sharing.
To use the Pathogenicity Calculator, you will need a valid login and password.