Next-Generation Sequencing for Schwannomatosis/Multiple Schwannoma Panel (SCH-NG)

Download Printer-Friendly PDF

Information for Ordering

Acceptable Specimen Types

• Fresh blood sample: 3–6 mL EDTA; no time limitations associated with receipt
• Saliva: OGD-575 DNA Genotek collection kit; kits are provided upon request
• DNA extracted from lymphocyte cells: minimum volume of 25 µL containing 3 µg of DNA; A₂₆₀/A₂₈₀ ratio ≥1.8; must be extracted in a CLIA-certified or equivalent laboratory
• Tumor specimens: A minimum of two anatomically distinct tumor specimens is recommended; however, a single tumor specimen may be submitted. Tumor specimens should contain at least 70% tumor content and greater than 80% nucleated cells.
  • Flash-frozen tumor shipped on dry ice
  • Fresh tumor or affected-tissue biopsy immersed in sterile culture media, such as PBS or RPMI
  • Formalin-fixed, paraffin-embedded tumor block with a surface area of at least 5 mm², or three to six loose paraffin curls measuring 30–50 µm thick; do not submit slides

Turnaround Time

• Blood, saliva, or DNA: Average of 30 working days
• Fresh or frozen tumor or tumor block: Average of 50 working days

Price, CPT Codes, and Z Code

• Institutional/self-pay price for blood, saliva, or DNA: $1,500 USD
• Institutional/self-pay price for fresh or frozen tumor or tumor block: $2,500 USD
• CPT codes: 81406, 81405, and 81479 × 3
• Z code: ZB67Y

Candidates for Testing

Patients with multiple schwannomas, with or without vestibular schwannomas. This testing approach is designed to evaluate for classic or mosaic NF2-related schwannomatosis, other forms of schwannomatosis, and mosaic schwannomatosis.

Specimen Shipping and Handling

Please refer to the specimen requirements listed above.

Specimens must be packaged to prevent breakage. Absorbent material must be included to contain liquids if breakage occurs. Specimens must also be shipped in double watertight containers, such as a specimen pouch placed inside the shipping company’s diagnostic envelope.

To request a collection kit, please complete the Collection Kit Request Form .

Please complete the Fresh/Frozen Tumor Submission Checklist when submitting tumor specimens.

Before shipping a specimen, please contact the UAB Medical Genomics Laboratory by email at medgenomics@uabmc.edu or by phone at 205-934-5562. Please provide the specimen type, shipment date, and package tracking number so the laboratory can help ensure proper and timely receipt.

Required Forms

• Test Requisition Form

About

Disorder Background

Schwannomas are nerve sheath tumors that are almost always benign but can cause significant pain. Although isolated schwannomas are relatively common, the development of multiple non-intradermal schwannomas (without bilateral vestibular schwannomas, congenital cataracts, or ependymomas typically associated with NF2-related schwannomatosis) is rare. Multiple non-intradermal schwannomas occurring in the absence of a family history of NF2-related schwannomatosis may result from mosaic NF2-related schwannomatosis or from germline pathogenic variants in SMARCB1 or LZTR1.

Individuals with LZTR1- or SMARCB1-related schwannomatosis do not typically develop bilateral vestibular schwannomas, ependymomas, meningiomas (features commonly associated with NF2-related schwannomatosis), neurofibromas, or astrocytomas (associated with NF1). However, clinical overlap does occur. Some individuals with SMARCB1-related schwannomatosis develop meningiomas or unilateral vestibular schwannomas, while some individuals with LZTR1-related schwannomatosis have been reported with unilateral or bilateral vestibular schwannomas. Schwannomatosis demonstrates variable expressivity. Penetrance for NF2-related schwannomatosis approaches 100%, whereas reduced penetrance has been documented in both LZTR1- and SMARCB1-related schwannomatosis.

Test Description

The Schwannomatosis/Multiple Schwannoma Panel by NGS simultaneously analyzes three genes: NF2, SMARCB1, and LZTR1. The assay uses a customized and optimized Agilent HaloPlex target enrichment system followed by paired-end Illumina sequencing. Each coding exon and approximately 50 base pairs of flanking intronic sequence are analyzed. The 5′ and 3′ untranslated regions are not included.

The average sequencing coverage exceeds 1,600×, with 100% of the coding regions covered at ≥350×. This depth of coverage enables detection of low-level mosaicism to approximately 3% variant allele fraction with 95% confidence. Sanger sequencing is performed as needed for confirmation.

Variant and copy number analysis are performed using a validated bioinformatics pipeline capable of detecting single nucleotide variants, small insertions and deletions, and indels up to 112 base pairs. Deletion/duplication analysis of NF2, SMARCB1, and LZTR1 is included because copy number variants are an established disease mechanism for these disorders.

Relevant family members of individuals with novel or previously identified variants of uncertain significance are offered targeted testing at no additional charge when appropriate clinical information is provided by a healthcare professional to assist with variant interpretation. There is no limit to the number of qualifying relatives who may be tested.

For patients with phenotypes that overlap among these disorders, analysis of associated tumor tissue may improve diagnostic accuracy.

Tumor-based analysis may be performed by next-generation sequencing on fresh, flash-frozen, or formalin-fixed paraffin-embedded (FFPE) tumor specimens. If the tumor specimen does not meet quality-control requirements for NGS, testing will reflex to Sanger sequencing when appropriate to provide results.

REFERENCES available here.

Other Related Test Options

• Next-Generation Sequencing and Deletion/Duplication Analysis of NF2 Only (NF2-NG)
• Rhabdoid Tumor Predisposition Syndrome by Next-Generation Sequencing (RT-NG)

For more information, test requisition forms, or collection kits, please contact the UAB Medical Genomics Laboratory at 205-934-5562 or medgenomics@uabmc.edu.

← Return to NF2, Meningiomas, Schwannomas, and Peripheral Nerve Sheath Tumors