With regards to test quality, various categories of next-generation sequencing (NGS) diagnostics are available (NGS Types A-C; see "Guidelines for diagnostic next generation sequencing" (Matthijs et al., Eur J Hum Genet. 2016 Jan;24(1):2-5).
Type A testing
This represents the highest standard level of quality possible with NGS. A detection precision of more than 99.9% and 100% coverage (at least 20-fold) of coding and flanking intronic regions (+/- 5 bp) is guaranteed. At the MGZ, this category currently includes the analysis of known, highly penetrant genes associated with clearly defined phenotypes (e.g., BRCA1, BRCA2, Duchenne / Becker-Kiener Muscular Dystrophy ID 20 and Hereditary Nonpolyposis Colon Cancer / Lynch Syndrome ID 99). These diagnostics are complemented by testing for genomic deletions and duplications and, if necessary, further analyses (e.g., homopolymer analyses, specific long-range PCR).
Type B testing
Analyses in this category include all of our gene panels that are sequenced with a detection precision of more than 99.9%. Our diagnostic criteria require a sequence depth of over 20 sequences per base pair in at least 98% of all analyzed regions. A table with information on individual regions with insufficient coverage is provided in each test report. If available, completion of single or multiple genes by Sanger sequencing and, if necessary, an additional deletion/duplication analysis of selected genes can be requested.
Type C testing
This quality category includes analyses such as the Clinical Exome (ID 112), and Whole Exome Sequencing (ID 165). Our diagnostic criteria require a sequence depth of over 20 sequences per base pair in at least 97% of all analyzed regions. Information on individual regions with insufficient coverage can be provided upon request but is not normally offered in standard test reports.
"Core" genes in human genetic diagnostics
"Core" genes refer to one or more clinical core symptoms and comprise all necessary genes that must be fully examined and evaluated in a diagnostic clarification in high quality. All "core" genes must be analysed with very high quality (consistently high quality parameters and generally complete technical coverage of the target region of at least 99% (Matthijs et al., Eur J Hum Genet. 2016 Jan;24(1):2-5)).