There continues to be a scientifically unjustified separation between efforts focused on interpretation of germline and somatic variants in cancer. In many cases, the importance of a germline variant in a tumor is revealed by a second somatic hit to that locus. Furthermore, evidence for pathogenicity of a variant in a germline context can be helpful in assessing its potential as a driver candidate when observed in a somatic context because biological function for that variant has been at least partially established. Similarly, if a germline variant is observed in a clinic as a VUS according to the ACMG guidelines but there is strong evidence for its recurrence in a somatic context, this again suggests biological function and increases its likelihood of pathogenicity. CIViC already has strong support for somatic variant evidence and basic support for integration of germline evidence. To enhance the synergistic use of these two broad categories of evidence we will develop integration approaches involving combined statistical models, somatic→germline and germline→somatic supporting evidence codes, detailed phenotypes, and visualizations to help leverage both germline and somatic evidence in assessing the clinical significance of variants.
There continues to be a scientifically unjustified separation between efforts focused on interpretation of germline and somatic variants in cancer. In many cases, the importance of a germline variant in a tumor is revealed by a second somatic hit to that locus. Furthermore, evidence for pathogenicity of a variant in a germline context can be helpful in assessing its potential as a driver candidate when observed in a somatic context because biological function for that variant has been at least partially established. Similarly, if a germline variant is observed in a clinic as a VUS according to the ACMG guidelines but there is strong evidence for its recurrence in a somatic context, this again suggests biological function and increases its likelihood of pathogenicity. CIViC already has strong support for somatic variant evidence and basic support for integration of germline evidence. To enhance the synergistic use of these two broad categories of evidence we will develop integration approaches involving combined statistical models, somatic→germline and germline→somatic supporting evidence codes, detailed phenotypes, and visualizations to help leverage both germline and somatic evidence in assessing the clinical significance of variants.