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  • Test code: 01461
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit
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Invitae Nervous System/Brain Cancer Panel

Test description

The Invitae Nervous System/Brain Cancer Panel analyzes genes associated with an increased lifetime risk of developing tumors of the brain, central and peripheral nervous systems. These genes were selected based on the available evidence to date to provide Invitae’s most comprehensive hereditary brain and nervous system cancers panel. Many of these genes are also associated with an increased risk of other cancer types.

The primary panel includes 27 genes associated with hereditary brain and nervous system cancers. In addition to the primary panel, clinicians can also choose to include 7 genes that have preliminary evidence of an association with these tumor types. At this time, the association remains uncertain; however, some clinicians may wish to include genes that may prove to be clinically significant in the future. These genes can be added at no additional charge.

Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.

PTEN: Deletion/duplication analysis covers the promoter region.

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Primary panel (27 genes)

AIP ALK APC DICER1 EPCAM HRAS LZTR1 MEN1 MLH1 MSH2 MSH6 NF1 NF2 PHOX2B PMS2 PRKAR1A PTCH1 PTEN RB1 SMARCA4 SMARCB1 SMARCE1 SUFU TP53 TSC1 TSC2 VHL

Add-on Preliminary-evidence Genes for Nervous System/Brain Cancer (7 genes)

Genes with preliminary evidence of an association with hereditary tumors of the brain and central and peripheral nervous systems are available to add on to the primary panel. Preliminary-evidence genes currently have early evidence of an association with the conditions covered by this test. Adding on preliminary-evidence genes can increase the number of variants of uncertain significance that are identified. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future. Visit our Preliminary-evidence genes page to learn more.

BAP1 BARD1 EZH2 GPC3 KIF1B POT1 PTCH2

Add-on Hereditary Paraganglioma-Pheochromocytoma Genes (8 genes)

Head and neck paragangliomas are neuroendocrine tumors that may occur in families with hereditary paraganglioma pheochromocytoma (PGL-PCC) syndrome. Clinicians can choose to include 8 genes that are associated with PGL-PCC at no additional charge.

MAX RET SDHA SDHAF2 SDHB SDHC SDHD TMEM127

  • Carney complex
  • constitutional mismatch repair deficiency syndrome (CMMR-D)
  • Cowden and Cowden-like syndrome
  • familial adenomatous polyposis (FAP)
  • familial isolated pituitary adenoma (FIPA)
  • familial neuroblastoma
  • Li-Fraumeni syndrome (LFS)
  • nevoid basal cell carcinoma (NBCS) – also known as Gorlin syndrome
  • neurofibromatosis type 1 (NF1)
  • neurofibromatosis type 2 (NF2)
  • Noonan syndrome
  • retinoblastoma
  • Rhabdoid tumor predisposition syndrome
  • schwannomatosis
  • Simpson-Golabi-Behmel syndrome (SGBS)
  • tuberous sclerosis complex (TSC)
  • von Hippel-Lindau syndrome (VHL)

The nervous system is a complex network of nerves and cells that carry messages to and from the brain and spinal cord to various parts of the body. The nervous system includes both the central nervous system (CNS) and peripheral nervous system (PNS). The CNS is composed of the brain and spinal cord; the PNS consists of the somatic and autonomic nervous systems.

A tumor can form within the cells and tissues that comprise the brain and nervous system, resulting in uncontrolled growth and the formation of a mass. These abnormal growths may be malignant or benign, could form in different areas of the nervous system throughout the body, can develop from different cell types, and may have different treatment options.

There are more than 120 kinds of nervous system tumors, including astrocytomas, atypical teratoid rhabdoid tumor (AT/RT), chondrosarcoma, choroid plexus, craniopharyngioma, ependymoma, germ cell tumor, glioblastoma, glioma, medulloblastoma, hemangioblastoma, meningioma, neurofibroma, schwannoma and malignant peripheral nerve sheath tumor, among others.

The general population risk for developing a CNS tumor is between 0.55%–0.69%. PNS tumors are rare in adults and children; CNS tumors are the most common cancers among children ages 0-19. Approximately 5% of CNS tumors are hereditary and due to a pathogenic variant; the remainder appear to be isolated and sporadic. Unlike sporadic cases, both hereditary CNS and PNS tumors may be syndromic and associated with extra-CNS features.

Individuals with a pathogenic variant in one of these genes have an increased risk of tumor development and/or malignancy compared to the average person, but not everyone with such a variant will actually develop cancer. Further, the same variant may manifest with different symptoms, even among family members. Because we cannot predict which cancers may develop, additional medical management strategies focused on cancer prevention and early detection may be beneficial. For gene-associated cancer risks, see the table below.

GeneCNS tumor typeRiskPNS tumor typeRiskOther
AIP Pituitary adenoma, 20-66% (PMID: 20506337)
ALK neuroblastoma, medulloblastoma elevated (PMID: 22810114, 22071890, 21972113)
APC medulloblastoma 1%–2% (PMID: 7661930)
DICER1 pituitary blastoma, pineoblastoma elevated (PMID: 25022261, 24839956)
EPCAM high-grade glioma, supratentorial primitive neuroectodermal tumors (PNET) 35% (PMID: 24737826, 24535705)
HRAS neuroblastoma elevated (PMID: 16443854, 22261753)
LZTR1 meningioma unknown schwannoma Elevated (PMID: 25480913, 24362817, 25335493)
MEN1 meningioma, spinal ependymoma, schwannoma elevated risk (PMID: 14871962)
MLH1 high-grade glioma, PNET 35% (PMID: 24737826, 24535705)
MSH2 high-grade glioma, supratentorial PNET 35% (PMID: 24737826, 24535705)
MSH6 high-grade glioma, supratentorial PNET 55% (PMID: 24737826, 24535705)
NF1   optic glioma, other CNS malignancies 15% (PMID: 24535705) malignant peripheral nerve sheath tumors, pheochromocytoma 10% (PMID: 24535705)
NF2 meningioma, spinal tumors 50%–75% (PMID: 24535705) bilateral vestibular schwannoma ~100% (PMID: 19652604)
PHOX2B neuroblastoma, ganglioneuroma, ganglioneuroblastoma 5%–6% (PMID: 16888290, 15657873)
PMS2 high-grade glioma, supratentorial PNET 60% (PMID: 24737826, 24535705)
PRKAR1A psammomatous melanotic schwannoma 10% (PMID:11549623)
PTCH1 medulloblastoma 5% (PMID: 9231911)
PTEN Lhermitte-Duclos (dysplastic gangliocytoma of the cerebellum) up to 32% (PMID: 20565722)
RB1 Retinoblastoma nearly 100% (PMID: 20301625, 8304343)
SMARCA4 atypical teratoid/rhabdoid tumor (AT/RT), schwannoma unknown (PMID: 25494491, 24535705) schwannoma unknown (PMID: 24535705)
SMARCB1 atypical teratoid/rhabdoid tumor (AT/RT), schwannoma elevated (PMID: 25494491, 24535705) schwannoma elevated (PMID: 24535705)
SMARCE1 clear cell meningioma unknown (PMID: 25249420, 25143307)
SUFU medulloblastoma elevated (PMID: 22508808, 19833601,12068298)
TP53 astrocytoma, glioblastoma, medulloblastoma, choroid plexus carcinoma elevated (PMID: 10864200, 20522432, 24535705)
TSC1 subependymal giant cell astrocytoma 6%–14% (PMID: 9568761)
TSC2 subependymal giant cell astrocytoma 6%–14% (PMID: 9568761)
VHL   hemangioblastoma 60%–80% (PMID: 21955200)

Elevated: There is evidence of association, but the penetrance and risk are not well characterized.
Unknown: Based on small studies, the risk is possibly increased, though not well-described.

The primary genes on this panel have an autosomal dominant inheritance pattern in association with the development of tumors of the brain and nervous system. The MLH1, MSH2, MSH6, and PMS2 genes are also associated with autosomal recessive constitutional mismatch repair deficiency syndrome (CMMR-D).

This panel may be considered for individuals whose personal and/or family history is suggestive of a hereditary nervous system tumor predisposition syndrome, including:

  • a brain tumor diagnosed under the age of 18
  • a brain tumor and:
    • hypopigmented skin lesions
    • consanguineous parents (parents who are related by blood)
    • a personal and/or family history of cancers and/or features associated with Lynch syndrome, Li-Fraumeni syndrome, tuberous sclerosis, neurofibromatosis type 1, or Gorlin syndrome
    • a second primary cancer
    • a sibling with a childhood cancer
  • an astrocytoma and melanoma in the same person or in two first-degree relatives
  • a medulloblastoma and ≥10 cumulative adenomatous colon polyps in the same person

There are also some common, general features suggestive of a hereditary cancer syndrome family. These include:

  • cancer diagnosed at an unusually young age
  • different types of cancer that have occurred independently in the same person
  • cancer that has developed in both of a set of paired organs (e.g., both kidneys, both breasts)
  • several close blood relatives that have the same type of cancer
  • unusual cases of a specific cancer type (e.g., breast cancer in a man)

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  2. Riegert-Johnson, DL, et al. Cancer and Lhermitte-Duclos disease are common in Cowden syndrome patients. Hered Cancer Clin Pract. 2010; 8(1):6. PMID: 20565722
  3. Cowan, R, et al. The gene for the naevoid basal cell carcinoma syndrome acts as a tumour-suppressor gene in medulloblastoma. Br. J. Cancer. 1997; 76(2):141-5. doi: 10.1038/bjc.1997.354. PMID: 9231911
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Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below, depending on the specific gene or test. In addition, the analysis covers select non-coding variants. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
AIP NM_003977.3
ALK NM_004304.4
APC* NM_000038.5
BAP1 NM_004656.3
BARD1 NM_000465.3
DICER1* NM_177438.2
EPCAM* NM_002354.2
EZH2* NM_004456.4
GPC3* NM_004484.3
HRAS NM_005343.2
KIF1B* NM_015074.3
LZTR1 NM_006767.3
MAX* NM_002382.4
MEN1* NM_130799.2
MLH1* NM_000249.3
MSH2* NM_000251.2
MSH6* NM_000179.2
NF1* NM_000267.3
NF2 NM_000268.3
PHOX2B* NM_003924.3
PMS2* NM_000535.5
POT1 NM_015450.2
PRKAR1A NM_002734.4
PTCH1 NM_000264.3
PTCH2 NM_003738.4
PTEN* NM_000314.4
RB1* NM_000321.2
RET NM_020975.4
SDHA* NM_004168.3
SDHAF2 NM_017841.2
SDHB NM_003000.2
SDHC* NM_003001.3
SDHD NM_003002.3
SMARCA4 NM_001128849.1
SMARCB1 NM_003073.3
SMARCE1 NM_003079.4
SUFU NM_016169.3
TMEM127 NM_017849.3
TP53* NM_000546.5
TSC1* NM_000368.4
TSC2 NM_000548.3
VHL NM_000551.3

APC: The 1B promoter region is covered by both sequencing and deletion/duplication analysis. The 1A promoter region is covered by deletion/duplication analysis. Sequencing analysis for exons 5 includes only cds +/- 10 bp.
DICER1: Sequencing analysis for exons 22 includes only cds +/- 10 bp.
EPCAM: Sequencing analysis is not offered for this gene.
EZH2: Sequencing analysis for exon 20 is limited to cds +/-10 bp.
GPC3: Sequencing analysis for exons 3 includes only cds +/- 10 bp.
KIF1B: Sequencing analysis for exons 20, 30 includes only cds +/- 10 bp.
MAX: Sequencing analysis for exons 2 includes only cds +/- 10 bp.
MEN1: Sequencing analysis for exons 2 includes only cds +/- 10 bp.
MLH1: Deletion/duplication analysis covers the promoter region. Sequencing analysis for exons 12 includes only cds +/- 10 bp.
MSH2: Analysis includes the exon 1-7 inversion (Boland mutation). Sequencing analysis for exons 2, 5 includes only cds +/- 10 bp.
MSH6: Sequencing analysis for exons 7, 10 includes only cds +/- 10 bp.
NF1: Sequencing analysis for exons 2, 7, 25, 41, 48 includes only cds +/- 10 bp.
PHOX2B: Alanine repeat numbers for the commonly-expanded region in exon 3 are not determined.
PMS2: Sequencing analysis for exons 7 includes only cds +/- 10 bp.
PTEN: Deletion/duplication analysis covers the promoter region. Sequencing analysis for exons 8 includes only cds +/- 10 bp.
RB1: Sequencing analysis for exons 15-16 includes only cds +/- 10 bp.
SDHA: Deletion/duplication analysis is not offered for this gene and sequencing analysis is not offered for exon 14. Sequencing analysis for exons 6-8 includes only cds +/- 10 bp.
SDHC: Sequencing analysis for exons 2, 6 includes only cds +/- 10 bp.
TP53: Deletion/duplication analysis covers the promoter region.
TSC1: Sequencing analysis for exons 21 includes only cds +/- 10 bp.