Test Information: This test has been designed to identify clinically significant genetic variants in a patient’s hematologic malignancies that may have therapeutic, prognostic, and/or diagnostic implications. This test targets the exons, which are the protein coding regions of 73 genes implicated in hematologic malignancies. Variants included on the report are limited to those classified as either Tier 1 , Tier 2, or Tier 3 with evidence towards somatic origin or with potential clinical significance.
Methodology: This test has been designed to assess variants occurring within protein coding regions and splice junctions of 73 RefSeq genes implicated in hematologic malignancies. Nucleic acid from the submitted specimen is enriched for coding and adjacent noncoding regions of the genes. The library products are sequenced with 2 by 150 bp reads on either the Illumina MiSeq, NextSeq or NovaSeq sequencing instruments ((Illumina, San Diego, CA). After alignment to the reference genome (GRCh37/hg19), off-target, low quality reads are removed from analysis and duplicate reads are tagged. The targeted regions are assessed for average depth of coverage and other data quality thresholds and variants are detected with several different variant calling algorithms. This test detects single nucleotide substitutions (SNVs), small insertions, deletions, and indels located in the coding sequences and known splice regions in the genes targeted by the test. Copy Number variants are not within scope of this test. Sequence alterations are described according to the Human Genome Variation Society (HGVS) nomenclature guidelines. Variants are classified according to the joint consensus recommendations for the interpretation and reporting of sequence variants in cancer by the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists Variants (PMID: 27993330). Variants with strong or potential clinical significance (Tier 1 and Tier 2 variants) and variants of unknown clinical significance (Tier 3 variants) are reported. Benign or likely benign variants (Tier 4 variants) are not reported.
Incidental findings are genetic changes that are of medical importance but that are not directly relevant to the indication for testing. Potential germline pathogenic variant (PGPV) is considered as one type of incidental findings. They are reported at the discretion of the laboratory and are only reported if they have significant healthcare implications for the patient.
The test was developed, and its performance characteristics were determined by Invitae. The report and methods used to generate the report, have not been cleared or approved by the U.S. Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. This test is used for both clinical and clinical research purposes. Pursuant to the requirements of federal regulations listed in the Clinical Laboratory Improvement Amendments of 1988 (CLIA), this laboratory has established and verified this test's accuracy and precision. However, the possibility of a false positive or false negative result incurred during any phase of the testing cannot be completely excluded. This report is based on data from this test only and reagents from single kits were used through the processing of the specimen in this report.
Gene list: ABL1, ANKRD26, ASXL1, ATRX, BCOR, BCORL1, BRAF, BTK, CALR, CBL, CBLB, CBLC, CCND2, CDKN2A, CEBPA, CSF3R, CUX1, CXCR4, DCK, DDX41, DHX15, DNMT3A, ETNK1, ETV6, EZH2, FBXW7, FLT3, GATA1, GATA2, GNAS, HRAS, IDH1, IDH2, IKZF1, JAK2, JAK3, KDM6A, KIT, KMT2A, KRAS, LUC7L2, MAP2K1, MPL, MYC, MYD88, NF1, NOTCH1, NPM1, NRAS, PDGFRA, PHF6, PPM1D, PTEN, PTPN11, RAD21, RBBP6, RUNX1, SETBP1, SF3B1, SH2B3, SLC29A1, SMC1A, SMC3, SRSF2, STAG2, STAT3, TET2, TP53, U2AF1, U2AF2, WT1, XPO1, ZRSR2
Limitations: A normal or inconclusive result does not eliminate the possibility of a genetic basis for disease in this individual and does not guarantee present or future health. Some types of genomic variants are not detectable by the technologies used to perform this test. This test is not intended to detect the following types of genetic variants: deletions/insertions of >15 bp, structural variation, variants in promotor regions and other non-coding regions, copy number variations, variations occurring within repetitive sequences and repeat expansion mutations, variants in regions with high homology or in genes with pseudogenes, mitochondrial genome mutations, epigenetic effects, mosaic events, and other complex aberrations. In addition, not all regions of the exome are fully covered by this analysis and variants in regions of low coverage may not be detected. This test is validated to report out variants with variant allele frequency of equal to or greater than 5%. Analytical sensitivity of >98.4% for insertions and > 99.9% for for SNVs and deletions, clinical sensitivity of > 99.9% were demonstrated in the test's validation studies.
The interpretation of this test is based on the assumption that the clinical information provided to the laboratory is accurate. Not all variants identified have been analyzed. In addition, the interpretation of these results is based on currently available scientific knowledge. Not all disease-associated genes have been identified and the clinical significance of variation in many genes is not well understood. Variant interpretation may change over time if more information becomes available. It is recommended that genetic test results be periodically reinterpreted. Healthcare providers can contact the laboratory to determine if there have been any changes to the interpretation of a variant or test result.
Although rare, the accuracy of results may also be impacted due to sample mix-up, DNA contamination, or poor DNA quality, as well as in the setting of bone marrow transplantation or a recent blood transfusion.
Laboratory Information: Inviate is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory (CAP#: 8289311; CLIA #31D2142534) located at 485F US Route 1 South, Suite 110, Iselin, NJ 08830.