Test Directory
VEXAS Genetic Panel by NGS
Justification
Specimen Requirements
| Sample Type | Volume Required | Minimum Volume | Stability | |
|---|---|---|---|---|
| PREFERRED | EDTA Whole Blood | 3mL | 1mL | Room Temp: 1 month; Refrigerated: 1 month |
| ALTERNATIVE | DNA previously extracted from a CLIA lab | - | - | - |
| REJECTION CRITERIA | Sample contamination; sample compromised; buccal or FFPE specimens |
| SPECIAL INSTRUCTIONS | If the patient has received a bone marrow transplant, call the lab for consultation before ordering. |
General Information
| METHODOLOGY | NGS |
| STAT TAT | < 48 hours (M-F) |
| STAT TAT Performance | > 90% of STAT results released in 48 hours |
| ROUTINE TAT | < 1 week |
| ALTERNATIVE NAMES | UBA1 gene sequencing |
| DESCRIPTION | 100% of the UBA1 exons plus 5-bp of intronic DNA flanking the exon-intron boundary are sequenced in this test. Machaon Diagnostics uses next-generation amplicon sequencing to rapidly detect all 22 single nucleotide variants and small insertions/deletions (indels) previously reported as associated with VEXAS. Novel, potentially pathogenic variants not previously reported would also be discovered. Sanger sequencing or orthogonal deep re-sequencing is used for verification of all novel somatic variants, and as needed for germline variants (i.e., a variant that fails to meet QC). The mean read depth is ~5000x and the limit of detection is a variant allele frequency of 2% or greater. The reference genome is Genome Reference Consortium Human Build 38 (GRCh38). Machaon Diagnostics uses an in-house database of variants from samples previously sequenced here plus variant data reported in the most up-to-date public databases and the published literature. For clarity, we do not report germline variants unless potentially novel or associated with our target diseases or disease risk modification in the literature. A minor allele frequency (MAF) of 0.01 indicates that the variant represents 1% of the alleles found in the population. All variants are available upon request. |
| LIMITATIONS | This test sequences 100% of every exon of the UBA1 gene, plus 5-bp of intronic DNA flanking the exon-intron boundary; this test would not detect pathogenic variants, if any, within promoter, deep intronic or untranslated regions (UTRs) or elsewhere in the genome. Rarely, diagnostic errors may occur due to primer-site variants or mismapping of sequences to homologous regions. Our reports are based on the current understanding of VEXAS syndrome. This understanding may change over time as new studies are published. We recommend annual follow-up for more current interpretations; call the lab to request (510-839-5600 ext 143). The panel may miss some structural variants such as inversions, translocations, deletions/duplications, and medium/large insertions; these types of structural variants are rare and challenging to detect for any clinical method without prior knowledge of the specific structural variant. Large copy number variants (deletions or duplications spanning multiple exons) may be detected by this method; however, this test is not currently validated to detect CNVs.
Natural chimeras (e.g., fusion of twin embryos in utero) and bone marrow transplant patients will be complicated candidates for this testing; please contact the lab for consultation before ordering. (Buccal swab is not an appropriate alternative specimen type for this somatic panel.) Other transplant patients (e.g., kidney, liver) and pregnant patients likely have non-self, cell-free DNA present in the blood; however, this cell-free DNA should not interfere with this testing. The clinical validation of this test did not include chimeras, transplant recipients or pregnant patients. Clonal hematopoiesis is a common aging-related phenomenon where a blood progenitor cell can contribute to a large genetically distinct subpopulation of blood cells and could be a source of essentially benign variants that may look suspicious. This effect is very age-dependent, observed in 10% of people > 65 years of age but in only 1% < 50 years of age. |
| NORMAL RANGE | Interpretation: Negative |
| ASSOCIATED TESTING | Cytokine Release Syndrome (12-test) Panel; Somatic Inborn Errors of Immunity (IEI) Genetic Panel |
| REFERENCES |
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| SAMPLE REPORT | Upon request |
| NEW YORK STATE APPROVED | NY Restricted Laboratory Permit Required |
Test Codes
| ORDER CODE | P1241 |
| CPT CODE | 81403 |
| LOINC CODE | 104268-8 |