Purpose/Principle

The CHCO Noonan Spectrum Disorders/RASopathies Panel utilizes next-generation sequencing technology to detect genomic variants in genes that are associated with RASopathies which is a group of phenotypically related but genetically heterogenous disorders including neurofibromatosis type 1, Noonan syndrome, Noonan syndrome with multiple lentigines, capillary malformation–arteriovenous malformation syndrome, Costello syndrome, cardio-facio-cutaneous syndrome, and Legius syndrome. The panel evaluates the coding regions and adjacent intronic bases of 26 genes for DNA variants. Copy number events are assessed by supplementing the exonic regions of interest with uniformly placed genomic hybridization probes.

The assay interrogates the coding regions and flanking intronic bases of the cited genes, with the capacity to detect sequence variants, and copy number variants (CNVs). Uniform genomic coverage is achieved through standardized specimen processing and short-read sequencing. Sequencing data are monitored by quality control metrics to ensure high confidence in the accuracy and specificity of the variant calls. The CNV resolution threshold is approximately 1 Mb, although smaller events may be detected depending on regional complexity and data quality.

BRAF, CBL, HRAS, KRAS, LZTR1, MAP2K1, MAP2K2, MAPK1, MRAS, NF1, NRAS, NSUN2, PPP1CB, PTPN11, RAF1, RASA2, RIT1, RRAS, RRAS2, RREB1, SHOC2, SOS1, SOS2, SPRED1, SPRED2, YWHAZ