• Test code: 01461
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit

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.

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Primary panel (27 genes)


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.


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.


  • 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)

  1. Hamilton, SR, et al. The molecular basis of Turcot's syndrome. N. Engl. J. Med. 1995; 332(13):839-47. doi: 10.1056/NEJM199503303321302. http://ncbi.nlm.nih.gov/pubmed/7661930 PMID: 7661930
  2. Switon, K, et al. Tuberous sclerosis complex: From molecular biology to novel therapeutic approaches. IUBMB Life. 2016; 68(12):955-962. PMID: 27797139
  3. Kimonis, VE, et al. Clinical and radiological features in young individuals with nevoid basal cell carcinoma syndrome. Genet. Med. 2013; 15(1):79-83. PMID: 22918513
  4. Omrani, H, et al. [Recurrent ovarian fibromas in condition of Gorlin syndrome]. J Gynecol Obstet Biol Reprod (Paris). 2010; 39(7):584-7. PMID: 20599329
  5. Veenstra-Knol, HE, et al. Early recognition of basal cell naevus syndrome. Eur. J. Pediatr. 2005; 164(3):126-30. PMID: 15717176
  6. Smith, MJ, et al. Vestibular schwannomas occur in schwannomatosis and should not be considered an exclusion criterion for clinical diagnosis. Am. J. Med. Genet. A. 2012; 158A(1):215-9. PMID: 22105938
  7. Mehta, GU, et al. Unilateral vestibular schwannoma in a patient with schwannomatosis in the absence of LZTR1 mutation. J. Neurosurg. 2016; 125(6):1469-1471. PMID: 26848914
  8. Bourdeaut, F, et al. Frequent hSNF5/INI1 germline mutations in patients with rhabdoid tumor. Clin. Cancer Res. 2011; 17(1):31-8. PMID: 21208904
  9. Lu-Emerson, C, Plotkin, SR. The neurofibromatoses. Part 2: NF2 and schwannomatosis. Rev Neurol Dis. 2009; 6(3):E81-6. PMID: 19898272
  10. Smith, MJ, et al. SMARCB1 mutations in schwannomatosis and genotype correlations with rhabdoid tumors. Cancer Genet. 2014; 207(9):373-8. PMID: 24933152
  11. Correa, R, et al. Carney complex: an update. Eur. J. Endocrinol. 2015; 173(4):M85-97. PMID: 26130139
  12. Ferner, RE, et al. Neurofibromatous neuropathy in neurofibromatosis 1 (NF1). J. Med. Genet. 2004; 41(11):837-41. PMID: 15520408
  13. Drouet, A, et al. Neurofibromatosis 1-associated neuropathies: a reappraisal. Brain. 2004; 127(Pt 9):1993-2009. PMID: 15289270
  14. Islam, MP, Roach, ES. Tuberous sclerosis complex. Handb Clin Neurol. 2015; 132:97-109. PMID: 26564073
  15. Hodgson, N, et al. Ophthalmic manifestations of tuberous sclerosis: a review. Clin. Experiment. Ophthalmol. 2017; 45(1):81-86. PMID: 27447981
  16. Jasperson, KW, Burt, RW. APC-Associated Polyposis Conditions. 1998 Dec 18. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: PMID: 20301519
  17. de, Kock, L, et al. Germ-line and somatic DICER1 mutations in pineoblastoma. Acta Neuropathol. 2014; 128(4):583-95. doi: 10.1007/s00401-014-1318-7. PMID: 25022261
  18. Asgharian, B, et al. Meningiomas may be a component tumor of multiple endocrine neoplasia type 1. Clin. Cancer Res. 2004; 10(3):869-80. PMID: 14871962
  19. Berry-Kravis, EM, et al. Congenital central hypoventilation syndrome: PHOX2B mutations and phenotype. Am. J. Respir. Crit. Care Med. 2006; 174(10):1139-44. PMID: 16888290
  20. Bleeker, FE, et al. Brain tumors and syndromes in children. Neuropediatrics. 2014; 45(3):137-61. PMID: 24535705
  21. Benn, DE, et al. Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes. J. Clin. Endocrinol. Metab. 2006; 91(3):827-36. PMID: 16317055
  22. Taylor, MD, et al. Mutations in SUFU predispose to medulloblastoma. Nat. Genet. 2002; 31(3):306-10. PMID: 12068298
  23. Brugières, L, et al. Incomplete penetrance of the predisposition to medulloblastoma associated with germ-line SUFU mutations. J. Med. Genet. 2010; 47(2):142-4. PMID: 19833601
  24. Brugières, L, et al. High frequency of germline SUFU mutations in children with desmoplastic/nodular medulloblastoma younger than 3 years of age. J. Clin. Oncol. 2012; 30(17):2087-93. PMID: 22508808
  25. Wilkie, AO. New germline syndrome with brainstem abnormalities and neuroblastoma, caused by ALK mutation. Hum. Mutat. 2011; 32(3):v. PMID: 21972113
  26. Coco, S, et al. Identification of ALK germline mutation (3605delG) in pediatric anaplastic medulloblastoma. J. Hum. Genet. 2012; 57(10):682-4. PMID: 22810114
  27. Evans, DG, et al. Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J. Med. Genet. 2002; 39(5):311-4. PMID: 12011145
  28. Stratakis, CA, et al. Clinical and molecular features of the Carney complex: diagnostic criteria and recommendations for patient evaluation. J. Clin. Endocrinol. Metab. 2001; 86(9):4041-6. PMID: 11549623
  29. Thomas, M, et al. Metastatic medulloblastoma in an adolescent with Simpson-Golabi-Behmel syndrome. Am. J. Med. Genet. A. 2012; 158A(10):2534-6. PMID: 22893378
  30. Diggs-Andrews, KA, et al. Sex Is a major determinant of neuronal dysfunction in neurofibromatosis type 1. Ann. Neurol. 2014; 75(2):309-16. PMID: 24375753
  31. 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
  32. Dow, G, et al. Spinal tumors in neurofibromatosis type 2. Is emerging knowledge of genotype predictive of natural history?. J Neurosurg Spine. 2005; 2(5):574-9. PMID: 15945431
  33. 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
  34. Reilly, KM. Brain tumor susceptibility: the role of genetic factors and uses of mouse models to unravel risk. Brain Pathol. 2009; 19(1):121-31. PMID: 19076777
  35. Chen, Y, et al. Oncogenic mutations of ALK kinase in neuroblastoma. Nature. 2008; 455(7215):971-4. PMID: 18923524
  36. Sredni, ST, Tomita, T. Rhabdoid tumor predisposition syndrome. Pediatr. Dev. Pathol. 2015; 18(1):49-58. doi: 10.2350/14-07-1531-MISC.1. PMID: 25494491
  37. Chompret, A, et al. P53 germline mutations in childhood cancers and cancer risk for carrier individuals. Br. J. Cancer. 2000; 82(12):1932-7. doi: 10.1054/bjoc.2000.1167. PMID: 10864200
  38. Hampel, H, et al. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet. Med. 2015; 17(1):70-87. doi: 10.1038/gim.2014.147. PMID: 25394175
  39. Bertherat, J. Carney complex (CNC). Orphanet J Rare Dis. 2006; 1:21. PMID: 16756677
  40. Torres, OA, et al. Early diagnosis of subependymal giant cell astrocytoma in patients with tuberous sclerosis. J. Child Neurol. 1998; 13(4):173-7. PMID: 9568761
  41. Wimmer, K, et al. Diagnostic criteria for constitutional mismatch repair deficiency syndrome: suggestions of the European consortium 'care for CMMRD' (C4CMMRD). J. Med. Genet. 2014; 51(6):355-65. doi: 10.1136/jmedgenet-2014-102284. PMID: 24737826
  42. Kimonis, VE, et al. Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Am. J. Med. Genet. 1997; 69(3):299-308. doi: 10.1002/(sici)1096-8628(19970331)69:3<299::aid-ajmg16>3.0.co;2-m. PMID: 9096761
  43. Wind, JJ, Lonser, RR. Management of von Hippel-Lindau disease-associated CNS lesions. Expert Rev Neurother. 2011; 11(10):1433-41. doi: 10.1586/ern.11.124. PMID: 21955200
  44. American Brain Tumor Association. Brain tumor statistics. https://www.abta.org/about-brain-tumors/brain-tumor-faqs/. Accessed September 2019.
  45. de, Kock, L, et al. Pituitary blastoma: a pathognomonic feature of germ-line DICER1 mutations. Acta Neuropathol. 2014; 128(1):111-22. doi: 10.1007/s00401-014-1285-z. PMID: 24839956
  46. Baysal, BE, Maher, ER. 15 years of paraganglioma: Genetics and mechanism of pheochromocytoma-paraganglioma syndromes characterized by germline SDHB and SDHD mutations. Endocr. Relat. Cancer. 2015; 22(4):T71-82. doi: 10.1530/ERC-15-0226. PMID: 26113606
  47. Ruijs, MW, et al. TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes. J. Med. Genet. 2010; 47(6):421-8. PMID: 20522432
  48. Brandi, ML, et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J. Clin. Endocrinol. Metab. 2001; 86(12):5658-71. doi: 10.1210/jcem.86.12.8070. PMID: 11739416
  49. Smith, MJ, et al. Germline mutations in SUFU cause Gorlin syndrome-associated childhood medulloblastoma and redefine the risk associated with PTCH1 mutations. J. Clin. Oncol. 2014; 32(36):4155-61. PMID: 25403219
  50. Smith, MJ, et al. Cranial meningiomas in 411 neurofibromatosis type 2 (NF2) patients with proven gene mutations: clear positional effect of mutations, but absence of female severity effect on age at onset. J. Med. Genet. 2011; 48(4):261-5. doi: 10.1136/jmg.2010.085241. PMID: 21278391
  51. Kerr, B, et al. Genotype-phenotype correlation in Costello syndrome: HRAS mutation analysis in 43 cases. J. Med. Genet. 2006; 43(5):401-5. doi: 10.1136/jmg.2005.040352. PMID: 16443854
  52. Walker, L, et al. A prospective study of neurofibromatosis type 1 cancer incidence in the UK. Br. J. Cancer. 2006; 95(2):233-8. doi: 10.1038/sj.bjc.6603227. PMID: 16786042
  53. Smith, MJ, et al. Germline SMARCE1 mutations predispose to both spinal and cranial clear cell meningiomas. J. Pathol. 2014; 234(4):436-40. PMID: 25143307
  54. Gadelha, MR, et al. Genetics of pituitary adenomas. Front Horm Res. 2013; 41:111-40. PMID: 23652674
  55. Lloyd, C, Grossman, A. The AIP (aryl hydrocarbon receptor-interacting protein) gene and its relation to the pathogenesis of pituitary adenomas. Endocrine. 2014; 46(3):387-96. PMID: 24366639
  56. Stiles, CE, Korbonits, M. Familial Isolated Pituitary Adenoma. 2016 Nov 11. In: Feingold, KR, et al, editors. Endotext (Internet). MDText.com, Inc.. PMID: 25905184
  57. Raverot, G, et al. Familial pituitary adenomas with a heterogeneous functional pattern: clinical and genetic features. J. Endocrinol. Invest. 2007; 30(9):787-90. PMID: 17993773
  58. Tichomirowa, MA, et al. High prevalence of AIP gene mutations following focused screening in young patients with sporadic pituitary macroadenomas. Eur. J. Endocrinol. 2011; 165(4):509-15. PMID: 21753072
  59. Vierimaa, O, et al. Pituitary adenoma predisposition caused by germline mutations in the AIP gene. Science. 2006; 312(5777):1228-30. PMID: 16728643
  60. Daly, AF, et al. Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families. J. Clin. Endocrinol. Metab. 2007; 92(5):1891-6. PMID: 17244780
  61. Beckers, A, Daly, AF. The clinical, pathological, and genetic features of familial isolated pituitary adenomas. Eur. J. Endocrinol. 2007; 157(4):371-82. PMID: 17893250
  62. Leontiou, CA, et al. The role of the aryl hydrocarbon receptor-interacting protein gene in familial and sporadic pituitary adenomas. J. Clin. Endocrinol. Metab. 2008; 93(6):2390-401. PMID: 18381572
  63. Igreja, S, et al. Characterization of aryl hydrocarbon receptor interacting protein (AIP) mutations in familial isolated pituitary adenoma families. Hum. Mutat. 2010; 31(8):950-60. PMID: 20506337
  64. Beckers, A, et al. Familial isolated pituitary adenomas (FIPA) and the pituitary adenoma predisposition due to mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. Endocr. Rev. 2013; 34(2):239-77. PMID: 23371967
  65. Paganini, I, et al. Expanding the mutational spectrum of LZTR1 in schwannomatosis. Eur. J. Hum. Genet. 2015; 23(7):963-8. PMID: 25335493
  66. Smith, MJ, et al. Mutations in LZTR1 add to the complex heterogeneity of schwannomatosis. Neurology. 2015; 84(2):141-7. PMID: 25480913
  67. Trochet, D, et al. PHOX2B genotype allows for prediction of tumor risk in congenital central hypoventilation syndrome. Am. J. Hum. Genet. 2005; 76(3):421-6. PMID: 15657873
  68. Gripp, KW, Lin, AE. Costello syndrome: a Ras/mitogen activated protein kinase pathway syndrome (rasopathy) resulting from HRAS germline mutations. Genet. Med. 2012; 14(3):285-92. doi: 10.1038/gim.0b013e31822dd91f. PMID: 22261753
  69. Raffalli-Ebezant, H, et al. Pediatric intracranial clear cell meningioma associated with a germline mutation of SMARCE1: a novel case. Childs Nerv Syst. 2015; 31(3):441-7. PMID: 25249420
  70. Piotrowski, A, et al. Germline loss-of-function mutations in LZTR1 predispose to an inherited disorder of multiple schwannomas. Nat. Genet. 2014; 46(2):182-7. PMID: 24362817
  71. Martins, R, Bugalho, MJ. Paragangliomas/Pheochromocytomas: clinically oriented genetic testing. Int J Endocrinol. 2014; 2014:794187. doi: 10.1155/2014/794187. PMID: 24899893
  72. Evans, DG. Neurofibromatosis 2 [Bilateral acoustic neurofibromatosis, central neurofibromatosis, NF2, neurofibromatosis type II]. Genet. Med. 2009; 11(9):599-610. doi: 10.1097/GIM.0b013e3181ac9a27. PMID: 19652604
  73. Korbonits, M, Kumar, AV. AIP-Related Familial Isolated Pituitary Adenomas. 2012 Jun 21. In: Adam, MP, et al, editors. GeneReviews® (Internet). University of Washington, Seattle. PMID: 22720333
  74. UpToDate Online. Risk factors for brain tumors. Accessed September 2019.
  75. UpToDate Online. Incidence of primary brain tumors. Accessed September 2019.
  76. National Library of Medicine, Genetics Home Reference: Gorlin syndrome. https://ghr.nlm.nih.gov/condition/gorlin-syndrome. Accessed September 2019.
  77. Seminog, OO, Goldacre, MJ. Risk of benign tumours of nervous system, and of malignant neoplasms, in people with neurofibromatosis: population-based record-linkage study. Br. J. Cancer. 2013; 108(1):193-8. PMID: 23257896
  78. Hulsebos, TJ, et al. Germline mutation of INI1/SMARCB1 in familial schwannomatosis. Am. J. Hum. Genet. 2007; 80(4):805-10. doi: 10.1086/513207. PMID: 17357086
  79. Thakker, RV, et al. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J. Clin. Endocrinol. Metab. 2012; 97(9):2990-3011. doi: 10.1210/jc.2012-1230. PMID: 22723327
  80. Maher, ER, et al. von Hippel-Lindau disease: a clinical and scientific review. Eur. J. Hum. Genet. 2011; 19(6):617-23. doi: 10.1038/ejhg.2010.175. PMID: 21386872
  81. van Leeuwaarde RS, et al. Von Hippel-Lindau Syndrome. 2000 May 17. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1463/ PMID: 20301636
  82. Evans, DG, Farndon, PA. Nevoid Basal Cell Carcinoma Syndrome. 2002 Jun 20. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1151/ PMID: 20301330
  83. Kool M, et al. Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. Cancer Cell. 2014 Mar 17;25(3):393-405. PMID: 24651015
  84. National Brain Tumor Society. Understanding brain tumors: http://braintumor.org/brain-tumor-information/understanding-brain-tumors/ Accessed September 2019.
  85. American Cancer Society, cancer.org: Lifetime Risks of Developing or Dying from Cancer, http://www.cancer.org/cancer/cancerbasics/lifetime-probability-of-developing-or-dying-from-cancer Accessed September 2019.
  86. Eng, C. Cancer: A ringleader identified. Nature. 2008; 455(7215):883-4. PMID: 18923503
  87. Bourdeaut, F, et al. ALK germline mutations in patients with neuroblastoma: a rare and weakly penetrant syndrome. Eur. J. Hum. Genet. 2012; 20(3):291-7. PMID: 22071890
  88. Janoueix-Lerosey, I, et al. Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma. Nature. 2008; 455(7215):967-70. PMID: 18923523
  89. Mossé, YP, et al. Identification of ALK as a major familial neuroblastoma predisposition gene. Nature. 2008; 455(7215):930-5. PMID: 18724359
  90. Park, JR, et al. Neuroblastoma: biology, prognosis, and treatment. Pediatr. Clin. North Am. 2008; 55(1):97-120, x. PMID: 18242317

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. In addition, the analysis covers the select non-coding variants specifically defined in the table below. 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.
EPCAM: Analysis is limited to deletion/duplication analysis.
MLH1: Deletion/duplication analysis covers the promoter region.
MSH2: Analysis includes the exon 1-7 inversion (Boland mutation).
PHOX2B: Alanine repeat numbers for the commonly expanded region in exon 3 are not determined.
SDHA: Deletion/duplication analysis is not offered for this gene. Sequencing analysis for exons 6-8, 14 includes only cds +/- 10 bp.
TP53: Deletion/duplication analysis covers the promoter region.