Download Neurome™ Neurological Exome Test Letter of

Neurome™ Neurological Exome Test Letter of Medical Necessity
<Date>
ATTN:
RE:
DOB:
Member ID:
Group #:
<Medical Director/ Physician Name>, MD
<Institution/Insurance Company>
<Street Address>
<City>, <State> <Zip>
<Patient Name>
<MM/DD/YYYY>
<Insurance ID Number>
<Enter Group #>
Dear Medical Director:
I am writing on behalf of my patient <Patient Name> to request coverage for the Neurome™ Neurological Exome
(Proband) test. This test is offered through Athena Diagnostics, Inc., and performed at Personalis, Inc., a highcomplexity CLIA-certified, CAP-accredited laboratory located in Menlo Park, CA. I have determined that this test is
medically necessary because of the following aspects of my patient’s history:
<Patient Name> is a <age> -year-old <gender > with a suspected neurogenetic disease because of the following
symptoms and clinical findings:
1. <Symptom #1 with ICD code>
2. <Symptom #2 with ICD code>
3. <Symptom #3 with ICD code>
< Add additional details if relevant >
The patient’s family history of similar conditions is <negative or unknown; add additional details if relevant>.
<Include the following paragraph if applicable>
This patient appears to have <genetic disorder that fulfills ACMG criterion>, as indicated by the symptoms above.
Additionally, other etiologies for the patient’s symptoms have been ruled out through past testing, including <past
testing here>.
Given the heterogeneous nature of rare genetic diseases, the most efficient way to confirm a genetic diagnosis in this
patient is to perform genetic testing with exome sequencing. Results from such testing may have a direct impact on
this patient’s treatment and management, and may provide critical prognostic information.
Current Clinical Practice
In 2012, the American College of Medical Genetics (ACMG) published a statement regarding the clinical application
of genomic sequencing, stating, “The ACMG recognizes that genomic sequencing approaches can be of great value
in the clinical evaluation of individuals with suspected germline genetic disorders…results will provide an explanation
for a patient’s phenotype by identifying a mutation in a gene known to be associated with the patient’s clinical
condition or in a gene that is highly likely to be causative given current knowledge.”1 The ACMG recommends exome
sequencing for the following indications:

The phenotype or family history data strongly implicate a genetic etiology, but the phenotype does not
correspond with a specific disorder for which a genetic test targeting a specific gene is available on a clinical
basis

A patient presents with a defined genetic disorder that demonstrates a high degree of genetic heterogeneity,
making whole exome sequencing (WES) or whole genome sequencing (WGS) analysis of multiple genes
simultaneously a more practical approach

A patient presents with a likely genetic disorder, but specific genetic tests available for that phenotype have
failed to provide a diagnosis

A fetus with a likely genetic disorder in which specific genetic tests, including targeted sequencing tests,
available for that phenotype have failed to indicate a diagnosis
In addition to the ACMG clinical practice guidelines, more recent studies have supported the exome sequencing
testing strategy through the identification of genes/diseases that were not recognized and would not have been
investigated through traditional single-gene or multi-gene panels.2,3 Exome sequencing has been used in a clinical
setting to find the molecular causes of a variety of diseases, including developmental delay2,4, inflammatory bowel
disease3, muscle weakness, and brain malformations5, among many others.4,6
Clinical Utility of Neurologic Exome Testing in this Patient
As mentioned above, knowledge of this patient's genetic information is important for me to more accurately assess
the prognosis and management plan. I am requesting the Neurome test because this patient has exhausted currently
available traditional diagnostic tests. The patient’s family and other medical providers have concerns regarding the
patient’s as-yet undiagnosed condition. A diagnosis can aid in determining the best course of treatment; identifying
necessary medical referrals to specialists; assessing the need for pre-symptomatic screening for associated
complications; eliminating unnecessary testing; formulating appropriate educational plans and patient advocacy; and
providing anticipatory guidance for families, including support group referrals, , carrier testing, and prenatal diagnosis.
<Include the following paragraph if additional family members will be submitted>
Comparing this individual’s exome sequence to additional family members' exomic data will increase the utility of the
test results and the likelihood of identifying a disease-causing, gene while decreasing the chance of obtaining
variants of unknown clinical significance. This method of evaluation is especially important for individuals with
apparently sporadic disease,4 when no one else in the family is similarly affected. By analyzing parents and
unaffected siblings in cases of sporadic disease, it is frequently possible to identify de novo or new mutations in the
child not present in either parent or to identify recessive diseases with one mutation inherited from each parent.
Neurome™ Neurological Exome Test
The Neurome™ Neurological Exome test is a robust exome sequencing test that targets the functionally relevant
regions of ~20,000 genes. Personalis’ proprietary exome sequencing technology incorporates enhanced sequencing
coverage of >8,000 biomedically relevant genes, including ~5,000 genes known to be associated with Mendelian
genetic disease, increasing the test’s sensitivity to detect variants in these genes. The Neurome test also includes
sequencing of known disease-causing variant positions located outside the coding regions of these genes (ie, outside
the “exome”).
In summary, I am requesting that <Patient Name> be approved for the Neurome™ Neurological Exome test, <#1500
for proband only, #1501 if additional family members sequenced>.. The CPT code for this test is <81415(1) for
proband only, 81415(1), 81416(1 or 2) if 1 or 2 additional family members are sequenced, respectively>. I hope you
will support my decision to perform the Neurome testing for this patient. Please feel free to contact me at <Physician
Phone> if you have additional questions.
Sincerely,
[Physician Signature and Name]
Sincerely,
<Physician Name>, MD
NPI #: <Physician NPI#>
Contact information:
< Address>
<City>, <State> <Zip>
Contact Phone No.: <phone number>
References
1.
ACMG Board of Directors. Points to consider in the clinical application of genomic sequencing. Genet Med
2012 Aug;14(8):759-61
2.
Dixon-Salazar TJ, Silhavy JL, Udpa N et al. Exome sequencing can improve diagnosis and alter patient
management. Sci Transl Med. 2012;4(138):138ra78.
3.
Worthey EA, Mayer AN, Syverson GD et al. Making a definitive diagnosis: successful clinical application of
whole-exome sequencing in a child with intractable inflammatory bowel disease. Genet Med. 2011;13:255–
262.
4.
Vissers LE, de Ligt J, Gilissen C et al. A de novo paradigm for mental retardation. Nat Genet. 2010;42:11091112.
5.
Pagnamenta AT, Lise S, Harrison V et al. Exome sequencing can detect pathogenic mosaic mutations
present at low allele frequencies; J Hum Genet. 2012;5:70-72.
6.
Yang Y, Muzny DM, Reid JG et al., Clinical Whole Exome Sequencing for the Diagnosis of Mendelian
Disorders. N Engl J Med. 2013;369(16):1502-1511.