ATTN: <Medical Director/ Physician Name, M.D.>

<Institution/Insurance Company>

<Street Address>

<City, State, Zip>

RE: <Patient Name>


MEMBER ID: <Insurance ID #>

Group #: <Group #>

Dear Medical Director:

I am writing on behalf of my patient <patient name> to request coverage for genetic testing with the Complete Tuberous Sclerosis Evaluation assay. This letter documents the medical necessity for genetic testing to confirm the diagnosis of tuberous sclerosis complex (TSC), and as such provides information about my patient’s medical and family history.

This test employs DNA sequencing and multiplex ligation-dependent probe amplification (MLPA) to identify TSC-associated mutations and deletions of the TSC1 and TSC2 genes. Results from the test will be used to help establish confirm the diagnosis and guide appropriate medical care.

I have determined that this test is medically necessary because of the following aspects of this patient’s history:

<Patient Name> is a <age>-year-old <gender> with a suspected diagnosis of TSC (<ICD-9 code(s)>) because of the following symptoms and clinical findings:

1. <Eg. Tuberous Sclerosis, ICD-9 code:>

2. <Eg. Autism Spectrum Disorder, ICD-9 code:>

3. <Eg. Infantile Spasms, ICD-9 code:>

4. <Eg. Facial Angiofibromas, ICD-9 code:>

5. <Eg. Angiomyolipomas, ICD-9 code:>

6. <Eg.additional relevant symptoms with ICD-9 codes:>

7. < Eg. Family history includes XX family member with similar symptoms >

Taken together, the clinical [[and family]] history is suggestive of TSC.

Rationale for Testing

Although many patients exhibit the first indications of TSC before age 1, it often remains undiagnosed for years.2 This is because definite clinical diagnosis of TSC requires the presence of at least 2 clinical features of disease, which may appear only over a period of several years or may be mild and non-specific (eg, hypomelanotic macules) and thus not a concern in isolation. Moreover, even severe presenting symptoms may be non-specific (e.g. intellectual disability, epilepsy, or autism spectrum disorder). A lack of family history is similarly indeterminate, as approximately two-thirds of TSC cases are sporadic.

Genetic testing can help confirm the diagnosis early on in patients whose clinical features are suggestive of TSC, and thus has potential to speed initiation of medical surveillance and delivery of appropriate management.1 According to current recommendations, detection of a pathogenic TSC1 or TSC2 mutation is diagnostic of TSC even in patients who do not meet clinical criteria.1

Athena’s Complete Tuberous Sclerosis Evaluation covers both genes known to be associated with TSC (TSC1 and TSC2) with 70% to 90% clinical sensitivity.1 The benefits of this test for my patient may include:

· Accurate genetic diagnosis

· Referral to a multidisciplinary TSC clinic that can provide comprehensive surveillance and management of the multi-system complications of TSC (which may include neurologic, cardiac, pulmonary, renal, and dermatologic complications).

· [[If the patient has epilepsy, add the following statement: “Guide antiepileptic use.2”]]

· [[If the patient has SEGAs, add the following statement: “Guide treatment of subependymal giant cell astrocytomas (SEGAs), a TSC-associated brain tumor for which there is an approved drug: Afinitor (everolimus; marketed by Novartis).]]

In short, the results of this genetic test will help determine the diagnosis so that I can proceed with the proper treatment and management. I am therefore requesting that <patient name> be approved for the Complete Tuberous Sclerosis Evaluation offered by Athena Diagnostics (test code 556; CPT codes: 81405 (x1), 81406 (x2), and 81407 (x1). I am specifying Athena Diagnostics to perform this test because Athena provides a highly specific and sensitive (>99% technical sensitivity) test with variant interpretation through its Athena Insight program. This program uses not only public databases, but an extensive proprietary database formed over years of testing to ascertain potential pathogenicity.

Please support my decision for genetic testing for epilepsy for <patient name>and feel free to contact me at <physician phone number>if you have additional questions.


<Physician Name>, <credentials>

NPI #: <NPI#>

Contact information: <Address if not on physician letterhead>

Contact Phone No.: <phone number>

Attachments: <Additional supporting documents>


1. Northrup H, Krueger DA. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 international tuberous sclerosis complex consensus conference. Pediatr Neurol. 2013;49:243-254.