XXXX multi-gene panel testing: comparison of two sequencing centers.

@entity1 @entity5344 @entity9517 @entity5345 @entity2674 @entity5962 @entity876 @entity9516
Multi-gene panels are used to identify genetic causes of @entity5344 ( @entity5344 ) in large @entity1 cohorts. This study compares the diagnostic workflow in two centers and gives valuable insights into different next-generation sequencing (NGS) strategies. Moreover, we present data from 620 @entity1 sequenced at both centers. Both sequencing centers are part of the German consortium for @entity5344 (GC- @entity5344 ). All 620 @entity1 included in this study were selected following standard @entity5345 /2 testing guidelines. A set of 10 sequenced genes was analyzed per @entity1 . Twelve samples were exchanged and sequenced at both centers. NGS results were highly concordant in 12 exchanged samples (205/206 variants = 99.51 %). One non-pathogenic variant was missed at center B due to a sequencing gap (no technical coverage). The custom enrichment at center B was optimized during this study; for example, the average number of missing bases was reduced by a factor of four (vers. 1: 1939.41, vers. 4: 506.01 bp). There were no sequencing gaps at center A, but four CCDS exons were not included in the enrichment. Pathogenic mutations were found in 12.10 % (75/620) of all @entity1 : 4.84 % (30/620) in @entity5345 , 4.35 % in @entity2674 (27/620), 0.97 % in @entity9516 (6/620), 0.65 % in ATM (4/620), 0.48 % in @entity5962 (3/620), 0.32 % in @entity9517 (2/620), 0.32 % in NBN (2/620), and 0.16 % in @entity876 (1/620). NGS diagnostics for @entity5344 -related genes is robust, cost effective, and the method of choice for genetic testing in large cohorts. Adding 8 genes to standard @entity5345 - and @entity2674 -testing increased the mutation detection rate by one-third.
