• 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



BAF47; CSS3; INI1; MRD15; PPP1R144; RDT; RTPS1; SNF5; SNF5L1; SWNTS1; Sfh1p; Snr1; hSNFS

Associated disorders

The SMARCB1 gene is associated with autosomal dominant rhabdoid tumor predisposition syndrome 1 (RTPS1) (MedGen UID: 322892), schwannomatosis (MedGen UID: 234775), and Coffin-Siris syndrome (MedGen UID: 766162).

The SMARCB1 gene is a tumor suppressor that encodes a subunit of the SWI/SNF complex, which regulates gene expression through chromatin remodeling.

SMARCB1—rhabdoid tumor predisposition syndrome
MedGen UID: 322892

Clinical condition
Rhabdoid tumors are rare, aggressive childhood cancers that most often develop in the kidney (called a malignant rhabdoid tumor [MRT]) and central nervous system (called an atypical/rhabdoid tumor [AT/RT]). These lesions can occur spontaneously or as part of hereditary rhabdoid tumor predisposition syndrome (RTPS) due to pathogenic variants in the SMARCB1 gene. In comparison to sporadic isolated rhabdoid tumors, RTPS is associated with an increased risk of developing multiple tumors at younger ages.

Rhabdoid tumors are very rare. Of all brain tumors diagnosed in children, approximately 1.5%–2.1% are AT/RT (PMID: 25886974) and MRTs account for 0.9%–2.0% of all renal cancers (PMID: 25886974). Most cases of rhabdoid tumors are isolated and non-syndromic, though an estimated 30%–35% of cases are due to RTPS (PMID: 22434719).

The SMARCB1 gene is also associated with schwannomatosis. Schwannomas are benign peripheral nerve sheath tumors, which present primarily in adulthood (PMD: 25494491). Schwannomatosis is a rare form of neurofibromatosis characterized by the development of multiple spinal, peripheral, and cranial-nerve schwannomas. Malignant transformation is rare. Some may also develop meningiomas (generally benign tumors of meningeal tissue). Life expectancy is normal; however, there can be significant morbidity depending upon the location of the schwannomas. The absence of vestibular schwannomas has traditionally distinguished schwannomatosis from neurofibromatosis type 2, however, there is evidence to suggest possible phenotypic overlap (PMID: 24933152, 19898272, 21208904, 17357086, 26848914, 22105938).

While an individual with a SMARCB1 pathogenic variant will not necessarily develop cancer in his/her lifetime, the risk for cancer is higher than that of the general population. The same SMARCB1 pathogenic variant can present differently, even among individuals within the same family. Lifetime cancer risks associated with pathogenic variants in SMARCB1 is currently unclear.

Gene information
SMARCB1 is a core component of the BAF (hSWI/SNF) complex. This ATP-dependent chromatin-remodeling complex plays important roles in cell proliferation and differentiation, cellular antiviral activities, and inhibition of tumor formation (UniProtKB – Q12824 (SNF5_HUMAN), Accessed July 2016). If there is a pathogenic variant in this gene that prevents it from functioning normally, the risk of developing certain types of cancers may be increased.

Pathogenic variants in SMARCB1 have autosomal dominant inheritance. This means that an individual with a pathogenic variant has a 50% chance of passing the condition on to their offspring. With this result, it is now possible to identify at-risk relatives who can pursue testing for this specific familial variant. Most cases occur spontaneously (i.e., an individual with a pathogenic variant has parents who do not have it) (PMID: 25060813, 25494491, 21108436).

RTPS-related management
Due to the rarity of RTPS, there is currently no clear consensus regarding a screening and surveillance protocol. However, it has been suggested that those with a pathogenic SMARCB1 variant consider the following surveillance regimen (PMID: 21210147):

  • Assess for central nervous system tumors by performing thorough physical and neurologic examinations and head ultrasound monthly during the first year of life.
  • Assess for renal lesions by performing abdominal ultrasound with a focus on the kidneys; for the first year of life, every 2–3 months, then every 6 months until 4 years of age.
  • Perform brain and spine MRIs every 6 months, beginning between 1 and 4 years of age.

Although no studies are currently available to validate the benefit of the proposed surveillance protocols, the aggressive nature of RTPS-related tumors suggests that screening may be beneficial (PMID: 21210147). Full medical management and surveillance guidelines are anticipated as more individuals are diagnosed.

Schwannomatosis-related management
There is currently no clear consensus regarding a screening and surveillance protocol for individuals with hereditary schwannomatosis. However, it has been suggested that the following management and surveillance be considered (PMID: 23701098, 23595180):

  • Observation of asymptomatic individuals (PMID: 17538359)
    • Self-monitoring for the development of new neurological symptoms (PMID: 23595180)
    • Regular and long-term follow-up is essential as fresh lesions may develop at any time (PMID: 23595180)
  • Brain MRI to rule-out intracranial tumors (PMID: 23595180)
    • High-resolution CT of temporal bone and internal auditory canals may be considered if MRI is contraindicated
  • MRI to assess peripheral schwannomas
    • CT and ultrasound may be alternatively considered depending on the clinical situation
  • Consider MRI evaluation of the spinal axis (PMID: 17219030)
  • Treat schwannoma-related pain similarly to neuropathic pain (PMID: 19898272, 16155448).
  • Surgical removal of symptomatic schwannomas and spinal cord compression, with no defined role for chemotherapy or radiation (PMID: 17538359, 16155448, 23595180)
  • Monitor asymptomatic tumors with serial MRI studies, suggested annually (PMID: 23595180)
    • The use of whole body MRI as a nonionizing radiation modality to monitor tumor growth is controversial (PMID: 19244040, 17219030)

An individual’s cancer risk and medical management are not determined by genetic test results alone. Overall cancer risk assessment incorporates additional factors, including personal medical history, family history, and any available genetic information that may result in a personalized plan for cancer prevention and surveillance.

Knowing if a pathogenic variant in SMARCB1 is present is advantageous. At-risk relatives can be identified, enabling pursuit of a diagnostic evaluation. Further, the available information regarding hereditary cancer susceptibility genes is constantly evolving and more clinically relevant data regarding SMARCB1 are likely to become available in the near future. Awareness of this cancer predisposition encourages patients and their providers to inform at-risk family members, to consider implementing proposed screening protocols, and to be vigilant in maintaining close and regular contact with their local genetics clinic in anticipation of new information.

Review date: July 2016

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
SMARCB1 NM_003073.3