Nathan D. Montgomery, Sara R. Selitsky, Nirali M. Patel, D

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Identification of Germline Variants in Tumor Genomic Sequencing Analysis Nathan D. Montgomery, Sara R. Selitsky, Nirali M. Patel, D. Neil Hayes, Joel S. Parker, Karen E. Weck The Journal of Molecular Diagnostics Volume 20, Issue 1, Pages 123-125 (January 2018) DOI: 10.1016/j.jmoldx.2017.09.008 Copyright © 2018 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

Figure 1 Density plots of allele fraction for germline variants in tumor and paired normal samples. Density plots are shown for the observed allele fraction of germline variants measured in tumor and paired normal samples from 1310 subjects. Light gray regions represent the area encompassed under both curves. For this analysis, variants detected in the paired normal sample were defined as germline variants. However, to be included in the study, variants were required to have a read depth of ≥100× in both tumor and normal samples. Approximately 6.8 million variants met these inclusion criteria. Somatic variants present only in the tumor sample are not included in this plot. VAF, variant allele fraction. The Journal of Molecular Diagnostics 2018 20, 123-125DOI: (10.1016/j.jmoldx.2017.09.008) Copyright © 2018 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

Figure 2 Comparison of variant allele fraction (VAF) of germline variants in tumor and paired normal samples. Observed VAF for germline variants in normal samples (x axis) and tumor samples (y axis). Results from a random sample of 100,000 variants (of 6.8 million total variants) are plotted for visualization. Among variants at 40% to 60% VAF in the normal sample, 78% are also detected at 40% to 60% VAF in tumor (boxed area), 10% were detected at >60% VAF in tumor (top dashed boxed area), and 11% were detected at <40% VAF in tumor (bottom dashed boxed area). The Journal of Molecular Diagnostics 2018 20, 123-125DOI: (10.1016/j.jmoldx.2017.09.008) Copyright © 2018 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions