• Test code: 01106
  • 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

Invitae Pediatric Nervous System/Brain Tumors Panel

Test description

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

Recent studies of pediatric cancer patients have reported predisposing pathogenic variants in a number of heritable genes. The results show that approximately 10% of children who develop cancer have an underlying cancer-predisposing condition. Genetic testing of these genes may confirm a diagnosis and can substantially influence the choice of appropriate screening and medical management options for the child and other 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.

Order test

Primary panel (26 genes)


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 eight genes that are associated with PGL-PCC at no additional charge.


Advances in genetic testing and studies of pediatric cancer patients have reported predisposing pathogenic genetic variants in a number of heritable genes. Identification of a hereditary cancer predisposition in childhood or adolescence can substantially influence the choice of appropriate screening and medical management options for the child and other relatives.

Although brain tumors are rare in the general population, they are the most common form of solid tumors among children under the age of 15, representing approximately 20% of all childhood cancers. Central nervous system (CNS) tumors are the most common cancers among children ages 0–19 years. Peripheral nervous system (PNS) tumors are rare in adults and children. Approximately 5%–10% of CNS tumors are hereditary and due to a pathogenic variant; the remainder are isolated and occur sporadically. Unlike sporadic cases, both hereditary CNS and PNS tumors may be syndromic and associated with features outside of the nervous system.

There are more than 120 types 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 tumors, among others.

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

Gene Condition Tumor types PMIDs/references
AIP Familial isolated pituitary adenoma (FIPA) pituitary adenoma 23371967, 22720333
ALK Familial neuroblastoma neuroblastoma 18724359, 18923523, 22071890, 18923503
APC Familial adenomatous polyposis (FAP) medulloblastoma 7661930
DICER1 DICER1 syndrome pituitary blastoma, pineoblastoma 25022261, 24839956
EPCAM Constitutional mismatch repair deficiency (CMMR-D) high-grade glioma, supratentorial primitive neuroectodermal tumors (PNET) 24737826, 24535705
HRAS Costello syndrome neuroblastoma 16443854, 22261753
LZTR1 Schwannomatosis schwannoma 25480913, 24362817, 25335493
MEN1 Multiple endocrine neoplasia type 1 (MEN1) meningioma, spinal ependymoma, schwannomas 14871962
MLH1 Constitutional mismatch repair deficiency (CMMR-D) high-grade glioma, supratentorial PNET 24535705, 24440087, 24737826, 24556086
MSH2 Constitutional mismatch repair deficiency (CMMR-D) high-grade glioma, supratentorial PNET 24535705, 24440087, 24737826, 24556086
MSH6 Constitutional mismatch repair deficiency (CMMR-D) high-grade glioma, supratentorial PNET 24535705, 24440087, 24737826, 24556086
NF1 Neurofibromatosis type 1 pheochromocytoma, optic glioma, neurofibromas, other CNS malignancies 24535705
NF2 Neurofibromatosis type 2 vestibular schwannoma, spinal schwannoma, meningioma 24535705, 19652604
PHOX2B Familial neuroblastoma neuroblastoma, ganglioneuroma, ganglioneuroblastoma 16888290, 15657873
PMS2 Constitutional mismatch repair deficiency (CMMR-D) high-grade glioma, supratentorial PNET 24535705, 24440087, 24737826, 24556086
PRKAR1A Carney complex psammomatous melanotic schwannoma 11549623
PTCH1 Basal cell nevus syndrome (Gorlin syndrome) medulloblastoma 9231911
PTEN PTEN hamartoma syndrome Lhermitte-Duclos (dysplastic gangliocytoma of the cerebellum) 20565722
RB1 Familial retinoblastoma retinoblastoma 20301625, 8304343
SMARCB1 Rhabdoid tumor predisposition syndrome, schwannomatosis rhabdoid tumors, schwannomas 22434719, 24933152, 21208904, 17357086
SMARCE1 Familial meningioma clear cell meningioma 25249420, 25143307
SUFU Basal cell nevus syndrome (Gorlin syndrome) medulloblastoma 22508808, 19833601,12068298
TP53 Li-Fraumeni syndrome astrocytoma, glioblastoma, medulloblastoma, choroid plexus carcinoma 10864200, 20522432, 24535705
TSC1 Tuberous sclerosis subependymal giant cell astrocytoma 9568761
TSC2 Tuberous sclerosis subependymal giant cell astrocytoma 9568761
VHL von Hippel Lindau syndrome hemangioblastoma 21955200

The majority of genes on this panel have an autosomal dominant hereditary predisposition to CNS and PNS tumors. The MLH1, MSH2, MSH6 and PMS2 genes are associated with autosomal recessive constitutional mismatch repair deficiency syndrome (CMMR-D).

Carriers of CMMR-D have an increased risk for adult-onset Lynch syndrome. This information will be included in the test report, when such variants are identified.

The Invitae Pediatric Nervous System/Brain Tumors Panel may be considered for children or young adults with the types of nervous system/brain tumors listed above or whose personal 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 or family history of cancers or features associated with Lynch syndrome, Li-Fraumeni syndrome, tuberous sclerosis complex, neurofibromatosis type 1 (NF1), or basal cell nevus (Gorlin) syndrome
    • a second primary cancer
    • a sibling with a childhood cancer
  • an astrocytoma and melanoma
  • two first-degree relatives with an astrocytoma and melanoma
  • a medulloblastoma and ≥10 cumulative adenomatous colon polyps

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. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. Heck, JE, et al. Epidemiology of rhabdoid tumors of early childhood. Pediatr Blood Cancer. 2013; 60(1):77-81. doi: 10.1002/pbc.24141. PMID: 22434719
  9. 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
  10. 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
  11. 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
  12. Vasen, HF, et al. Guidelines for surveillance of individuals with constitutional mismatch repair-deficiency proposed by the European Consortium Care for CMMR-D" (C4CMMR-D). J. Med. Genet. 2014; 51(5):283-93. doi: 10.1136/jmedgenet-2013-102238. " PMID: 24556086
  13. 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
  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. 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
  21. 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
  22. 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
  23. 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
  24. Smith, MJ, et al. Mutations in LZTR1 add to the complex heterogeneity of schwannomatosis. Neurology. 2015; 84(2):141-7. PMID: 25480913
  25. Paganini, I, et al. Expanding the mutational spectrum of LZTR1 in schwannomatosis. Eur. J. Hum. Genet. 2015; 23(7):963-8. PMID: 25335493
  26. Park, JR, et al. Neuroblastoma: biology, prognosis, and treatment. Pediatr. Clin. North Am. 2008; 55(1):97-120, x. PMID: 18242317
  27. Mossé, YP, et al. Identification of ALK as a major familial neuroblastoma predisposition gene. Nature. 2008; 455(7215):930-5. PMID: 18724359
  28. 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
  29. 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
  30. Eng, C. Cancer: A ringleader identified. Nature. 2008; 455(7215):883-4. PMID: 18923503
  31. 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
  32. Lohmann, DR, Gallie, BL. Retinoblastoma. 2000 Jul 18. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301625
  33. 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
  34. 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
  35. Bertherat, J. Carney complex (CNC). Orphanet J Rare Dis. 2006; 1:21. PMID: 16756677
  36. 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
  37. 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
  38. 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
  39. 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
  40. 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
  41. 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
  42. Evans, DG, et al. Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J. Med. Genet. 2002; 39(5):311-4. PMID: 12011145
  43. Coco, S, et al. Identification of ALK germline mutation (3605delG) in pediatric anaplastic medulloblastoma. J. Hum. Genet. 2012; 57(10):682-4. PMID: 22810114
  44. Wilkie, AO. New germline syndrome with brainstem abnormalities and neuroblastoma, caused by ALK mutation. Hum. Mutat. 2011; 32(3):v. PMID: 21972113
  45. 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
  46. 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
  47. Taylor, MD, et al. Mutations in SUFU predispose to medulloblastoma. Nat. Genet. 2002; 31(3):306-10. PMID: 12068298
  48. Benn, DE, et al. Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes. J. Clin. Endocrinol. Metab. 2006; 91(3):827-36. PMID: 16317055
  49. Bleeker, FE, et al. Brain tumors and syndromes in children. Neuropediatrics. 2014; 45(3):137-61. PMID: 24535705
  50. 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
  51. 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
  52. Mody, RJ, et al. Integrative Clinical Sequencing in the Management of Refractory or Relapsed Cancer in Youth. JAMA. 2015; 314(9):913-25. PMID: 26325560
  53. Zhang, J, et al. Germline Mutations in Predisposition Genes in Pediatric Cancer. N. Engl. J. Med. 2015; 373(24):2336-46. PMID: 26580448
  54. Plon, SE, Nathanson, K. Inherited susceptibility for pediatric cancer. Cancer J. 2005; 11(4):255-67. PMID: 16197716
  55. Knapke, S, et al. Identification, management, and evaluation of children with cancer-predisposition syndromes. Am Soc Clin Oncol Educ Book. 2012; :576-84. PMID: 24451799
  56. Naumova, A, Sapienza, C. The genetics of retinoblastoma, revisited. Am. J. Hum. Genet. 1994; 54(2):264-73. PMID: 8304343
  57. Chen, Y, et al. Oncogenic mutations of ALK kinase in neuroblastoma. Nature. 2008; 455(7215):971-4. PMID: 18923524
  58. Hodgson, N, et al. Ophthalmic manifestations of tuberous sclerosis: a review. Clin. Experiment. Ophthalmol. 2017; 45(1):81-86. PMID: 27447981
  59. Islam, MP, Roach, ES. Tuberous sclerosis complex. Handb Clin Neurol. 2015; 132:97-109. PMID: 26564073
  60. Drouet, A, et al. Neurofibromatosis 1-associated neuropathies: a reappraisal. Brain. 2004; 127(Pt 9):1993-2009. PMID: 15289270
  61. Ferner, RE, et al. Neurofibromatous neuropathy in neurofibromatosis 1 (NF1). J. Med. Genet. 2004; 41(11):837-41. PMID: 15520408
  62. Correa, R, et al. Carney complex: an update. Eur. J. Endocrinol. 2015; 173(4):M85-97. PMID: 26130139
  63. Smith, MJ, et al. SMARCB1 mutations in schwannomatosis and genotype correlations with rhabdoid tumors. Cancer Genet. 2014; 207(9):373-8. PMID: 24933152
  64. Lu-Emerson, C, Plotkin, SR. The neurofibromatoses. Part 2: NF2 and schwannomatosis. Rev Neurol Dis. 2009; 6(3):E81-6. PMID: 19898272
  65. Bourdeaut, F, et al. Frequent hSNF5/INI1 germline mutations in patients with rhabdoid tumor. Clin. Cancer Res. 2011; 17(1):31-8. PMID: 21208904
  66. 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
  67. 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
  68. Veenstra-Knol, HE, et al. Early recognition of basal cell naevus syndrome. Eur. J. Pediatr. 2005; 164(3):126-30. PMID: 15717176
  69. 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
  70. 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
  71. Switon, K, et al. Tuberous sclerosis complex: From molecular biology to novel therapeutic approaches. IUBMB Life. 2016; 68(12):955-962. PMID: 27797139
  72. 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
  73. 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
  74. 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
  75. 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
  76. 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
  77. Bakry, D, et al. Genetic and clinical determinants of constitutional mismatch repair deficiency syndrome: report from the constitutional mismatch repair deficiency consortium. Eur. J. Cancer. 2014; 50(5):987-96. doi: 10.1016/j.ejca.2013.12.005. PMID: 24440087
  78. Martins, R, Bugalho, MJ. Paragangliomas/Pheochromocytomas: clinically oriented genetic testing. Int J Endocrinol. 2014; 2014:794187. doi: 10.1155/2014/794187. PMID: 24899893

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
DICER1* NM_177438.2
EPCAM* NM_002354.2
HRAS NM_005343.2
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
PRKAR1A NM_002734.4
PTCH1 NM_000264.3
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
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.
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.