Table 2. Pathogenic Germline Variants Missed by Tumor Testing.

No.	Likely reason for differencea
13	Gene not in the tumor testb
14	Technical limitation with tumor testc 5 Small copy number deletion (2-3 exons) 4 Large or complex insertion or deletion 3 Variant in a pseudogene-associated region (PMS2) 1 Intronic pathogenic variant 1 Allele dropout in amplicon sequencing
11	Variant interpretation differenced
12	Unknown reasone
50	Total

^a Details are provided in eTable 2 in the Supplement.

^b In the case of hotspot assays (n = 2), the region of the gene containing the variation was not sequenced in the tumor.

^c Technical limitations detecting variants of these types are expected in tumor tests.

^d All of these variants met guidelines¹⁶ to be considered pathogenic in germline DNA. These variants, however, may not have met guidelines¹⁷ to be considered clinically significant if assumed incorrectly to be somatic. Most (n = 9) were missense variants that can require significant effort to research and interpret thoroughly.

^e Inadequate details were provided by the ordering clinician or tumor sequencing laboratory to determine a likely reason for the difference.