Beyond DNA: An Integrated and Functional Approach for Classifying Germline Variants in Breast Cancer Genes

Figure 1

An integrated approach for variant classification. Lines of evidence such as structural function, RNA studies, and functional studies assess the functional impact on the mRNA and protein. Cooccurrence, segregation, case-control studies, and the observed phenotype in variant carriers reflect the pathogenicity of a variant. Population frequency, in silico models, and evolutionary conservation assess fitness of the amino acid or nucleotide position.