Test Directory
CoagGenex Clotting Genetic Panel
Justification
Specimen Requirements
| Sample Type | Volume Required | Minimum Volume | Stability | |
|---|---|---|---|---|
| PREFERRED | EDTA Whole Blood | 3mL | 1mL | Room Temp.: 1 month Refrigerated: 1 month |
| ALTERNATIVE | Cheek swab | 2 swab | - | Room Temp.: 1 month Refrigerated: 1 month |
| REJECTION CRITERIA | Sample contamination; sample compromised |
| SPECIAL INSTRUCTIONS | - |
General Information
| METHODOLOGY | NGS |
| STAT TAT | < 48 hours (M-F) |
| STAT TAT Performance | > 90% of results released in 48 hours |
| ROUTINE TAT | < 5 days (M-F) |
| ALTERNATIVE NAMES | Hypercoagulability Genetic Panel, Hypercoag Genetic Panel, Inherited Thrombophilia |
| DESCRIPTION | 28 genes associated with thrombophilia plus variants in CYP2C9, the CYP2C cluster, and VKORC1 for characterizing warfarin sensitivity: ADAMTS13, CBS, F1 (FGA), F1 (FGB), F1 (FGG), F11, F12, F13A1, F13B, F2, F5, F7, F8, F9, HRG, MAST2, PLAT, PLG (plasminogen), PROC (protein C), PROCR, PROS1 (protein S), SERPINC1 (antithrombin III), SERPIND1, SERPINE1 (PAI-1), STAB2, TFPI, THBD, and VWF; plus CYP2C9, the CYP2C cluster, and VKORC1 for warfarin sensitivity. DNA sequences were compared to the reference Human genome (Hg38) sequence. Machaon Diagnostics maintains a Thrombophilia Genetic Database of pathogenic variants, disease-associated and benign polymorphisms, and other known variants of undetermined significance. This database is actively updated as new mutations are identified or reported in public databases and the literature. Machaon Diagnostics employs a next-generation amplicon sequencing technique (patent pending) that allows for the rapid detection (48 hours) of mutations, small insertions/deletions and polymorphisms that have been previously reported as associated with thrombophilia. This assay may also discover novel, deleterious variants not previously known which will be reported as such. This panel includes all genes in the “thrombosis” category of the curated disease-causing genes for bleeding, thrombotic, and platelet disorders, published by the International Society on Thrombosis and Haemostasis. MTHFR is also sequenced, but in keeping aligned with the most up-to-date guidelines from relevant advisory groups (e.g., ACMG and WTD Steering Committee), we will not report these variants unless requested by the ordering physician. This panel also detects the CYP2C9, CYP2C cluster and VKORC1 polymorphisms affecting warfarin sensitivity, which is an anticoagulant frequently used to treat or prevent VTE. |
| LIMITATIONS | This test targets all exons of the selected 28 genes, plus 5bp of intronic DNA flanking the exon-intron boundary, and the polymorphisms in CYP2C9, the CYP2C cluster and VKORC1 underlying warfarin sensitivity. This test would not detect a pathogenic variant within a promoter or deep intronic regions or elsewhere in the genome unless it was part of the subset we specifically targeted based on the published literature. A rare variant disrupting primer binding during PCR could potentially lead to a false negative. As a general rule, medium sized duplications and heterozygous deletions (~100bp to tens of kbp) are difficult to detect by NGS. Homozygous deletions are relatively easy to detect because the coverage at the affected amplicon(s) will drop to zero (as opposed to dropping by half, in the case of a heterozygous deletion, which can be masked by noise). NGS will likely miss chromosomal inversions and translocations unless the breakpoints are already known and being specifically targeted. Warfarin-sensitivity star allele assignment is limited by the loci covered by this test. Rare sequence variants, including in genes not covered by this test, with previously-uncharacterized functional significance may impact warfarin metabolism and activity. Allele assignments for CYP2C9 depend on assumptions about the phase of variants. |
| NORMAL RANGE | Interpretation: Negative |
| ASSOCIATED TESTING | - |
| REFERENCES | Dautaj A, et al. Hereditary thrombophilia. Acta Biomed. 2019 Sep 30;90(10-S):44-46. |
| SAMPLE REPORT | Upon request |
| NEW YORK STATE APPROVED | No |
Test Codes
| ORDER CODE | P1227 |
| CPT CODE | 81406, 81407, 81479x27 |
| LOINC CODE | see individual genes |