Invitae Schwannomatosis Test


Test description

The Invitae Schwannomatosis Test analyzes the tumor suppressor gene SMARCB1, which is associated with schwannomatosis.

Testing should be considered in any individual with multiple schwannomas or a family history of schwannomatosis. Individuals inheriting a pathogenic variant are at increased risk of developing multiple schwannomas, primarily along peripheral nerves, that often cause chronic, severe pain and, at times, debilitation. This test can also distinguish schwannomatosis from NF2 prior to the development of vestibular schwannomas. In NF2, vestibular schwannomas usually develop by age 30 and are a hallmark of the disease, but they are absent in schwannomatosis. Medical management, natural history, treatment, mortality, and genetic risks differ greatly between schwannomatosis and NF2, so distinguishing the two phenotypes is of critical importance.

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Primary panel (1 gene)


Add-on neurofibromatosis type 2 gene (1 gene)

Individuals with multiple schwannomas may eventually fulfill NF2 diagnostic criteria and some simplex cases of schwannomatosis are mosaic for a pathogenic NF2 variant. This gene can be added to this test for no additional charge.



Schwannomatosis is a rare form of neurofibromatosis that results in multiple schwannomas (a benign myelin sheath tumor derived from Schwann cells). Schwannomas arise primarily along the peripheral nerves but they can also appear along intracranial nerves and/or the spinal nerve root. Schwannomatosis is distinguished from neurofibromatosis type 2 (NF2) in that there are no concomitant bilateral vestibular schwannomas—a diagnostic criterion of NF2.

Affected schwannomatosis patients generally present in the second or third decade of life with chronic, severe pain (although pain intensity varies between individuals) and neurologic dysfunction if the schwannoma is pressing on a nerve or nearby tissue. Overall, symptomatology is widely variable and is dependent upon where schwannomas are located. Additional symptoms can include tingling, weakness due to nerve or spinal cord compression, difficulty with urination or bowel dysfunction, facial weakness, headaches, vision changes, and lumps or swollen areas where tumors form under the skin. Malignant transformation rarely occurs. Some patients may also develop meningiomas (generally benign tumors of meningeal tissue). Up to one third of schwannomatosis patients present with a segmental or mosaic form, in which schwannomas are localized to one limb or five or fewer spinal segmental segments. Life expectancy is normal, but there can be significant morbidity depending upon the location of the schwannomas.

Mutations in the SMARCB1 gene occur in 40%-50% of familial cases and 8%-10% of sporadic cases of schwannomatosis. This test will identify mutations in up to 60% of mutation-positive individuals with a clinical diagnosis of schwannomatosis. It is difficult to more definitively describe the sensitivity of this test in individuals with schwannomatosis, as a majority of sporadic schwannomatosis patients, as well as individuals with multiple meningiomas, have no known causative mutation.

Single schwannomas occur frequently in the general population and these cases are generally sporadic. The inheritance of multiple schwannomas (schwannomatosis) is not well understood and only about 15%-25% of those cases are considered hereditary. Hereditary forms exhibit autosomal dominant inheritance, highly variable expressivity, and incomplete penetrance.

Schwannomatosis exhibits highly variable expressivity and incomplete penetrance.

The exact incidence of inherited schwannomatosis is not definitively known, but it may be as common as neurofibromatosis type 2, which affects approximately 1 in 40,000 births. There is no known predilection for race or gender.

Testing for schwannomatosis may be indicated in an individual with a family history of multiple schwannomas in a first-degree relative or for diagnostic confirmation in a proband. Current diagnostic criteria for schwannomatosis, published in the American Journal of Medical Genetics Part A, are as follows:

Clinical diagnosis:

  • The individual has two or more non-intradermal schwannomas, one with pathological confirmation, including no bilateral vestibular schwannoma by high-quality MRI (detailed study of internal auditory canal with slices no more than 3 mm thick); Some mosaic NF2 patients will be included in this diagnosis at a young age and some schwannomatosis patients have been reported to have unilateral vestibular schwannomas or multiple meningiomas.
  • The individual has one pathologically confirmed schwannoma or intracranial meningioma and an affected first-degree relative.
  • Consider schwannomatosis as a possible diagnosis if there are two or more non-intradermal tumors but none has been pathologically proven to be a schwannoma. The occurrence of chronic pain in association with the tumor(s) increases the likelihood of schwannomatosis.

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, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
NF2 NM_000268.3
SMARCB1 NM_003073.3