LETTER OF MEDICAL NECESSITY FOR CLINICAL EXOME SEQUENCING (ExomeNext)
Date:
Date of service/claim
To:
Utilization Review Department
Insurance Company Name, Address, City, State
Re:
Patient Name, DOB, ID #
ICD-9 Codes: (list codes)
This letter is in regards to my patient and your subscriber, First, Last Name, requesting full coverage of
medically-indicated genetic testing for clinical exome sequencing to be performed by Ambry Genetics
Corporation (TIN 33-0892453 / NPI 1861568784), a CAP-approved and CLIA-certified laboratory located
at 15 Argonaut, Aliso Viejo, CA 92656.
Approximately 85% of genetic changes that cause known diseases occur within the exome – the set of
protein-coding regions that is about 1-2% of the entire human genome.1 Whole exome sequencing has been
shown to be a successful option for diagnosing individuals with previously unidentified genetic conditions.2
The American College of Medical Genetics and Genomics published a 2012 Policy Statement on the clinical
application of genomic sequencing.3 The statement recommends exome sequencing for the following
clinical scenarios (adapted from original publication):

The patient’s clinical presentation (phenotype) and family history strongly implicate a genetic etiology, but
phenotype does not correspond with a specific disorder for which a clinical targeted genetic test is available
Clinical presentation (including fetal, with limitations) suggests a likely genetic disorder, but specific genetic tests
(including targeted sequencing tests) for phenotype have failed to provide a diagnosis
A defined genetic disorder with a high degree of genetic heterogeneity is suspected, making whole exome or
genome sequencing of multiple genes simultaneously a more practical approach


Significant aspects of my patient’s personal and/or family medical history that raise reasonable
suspicion of an underlying genetic diagnosis are as follows:



Based on the above, I suspect my patient could have:


 Syndrome X (for which a genetic etiology is highly suspected, but yet to be discovered)
In order to evaluate for the above conditions, my patient has had the following uninformative tests:



Due to the heterogeneous nature of my patient’s symptoms and uninformative test results thus far,
there is a reasonable probability of detecting a genetic mutation using this test. Per ACMG
guidelines, clinical exome sequencing is warranted for my patient.3
This test (ExomeNext) thoroughly analyzes the exome and mitochondrial genome, with extensive results
analysis and interpretation. I am choosing ExomeNext because of its diagnostic rates as compared to other
options in the industry,4 and because is a highly efficient and cost-effective way to analyze the functionally
relevant regions in our 20,000 genes.
Clinical exome sequencing has a significant likelihood of providing my patient and his/her family
with an accurate diagnosis, thereby ensuring appropriate medical management. In many cases, a
diagnosis can lead to a specific treatment or management strategy that dramatically changes the clinical
outcome.2,5 A diagnosis can also help identify necessary medical referrals, screening for associated
complications, and recurrence risk counseling.2,5 Once a diagnosis is made, the costs associated with further
testing are likely to decrease.2,5 Due to these benefits, exome sequencing is medically warranted in my
patient. As such, I am ordering this medically necessary test and affirm that my patient has provided
informed consent for genetic testing.
A positive test result would confirm a genetic diagnosis and/or risk in my patient, and would ensure my
patient is being managed appropriately. I am specifying Ambry Genetics Corporation because this
laboratory was the first to commercially offer clinical exome sequencing, and does so in a highly-sensitive
and cost-effective manner. It also has a large database of tested patients to ensure highly validated,
accurate, and informative test interpretation.
I recommend that you support this request for coverage of clinical exome sequencing in my patient.
Depending on the exact test ordered, genetic testing can take up to several months to complete and the
laboratory will not bill until testing is concluded. Therefore, we are requesting that the authorization be
valid for 12 months.
Thank you for your time and please don’t hesitate to contact me with any questions.
Sincerely,
Ordering Clinician Name (Signature Provided on Test Requisition Form)
(MD/DO, Clinical Nurse Specialist, Nurse-Midwives, Nurse Practitioner, Physician Assistant, Genetic
Counselor*)
*Authorized clinician requirements vary by state
Test Details
CPT codes:
81404x2, 81405x2, 81406x2, 81407x2, 81408x2
Laboratory:
Ambry Genetics Corporation (TIN 33-0892453 / NPI 1861568784), a CAP-accredited and
CLIA-certified laboratory located at 15 Argonaut, Aliso Viejo, CA 92656
References:
1.
2.
3.
4.
5.
Pussegoda KA. Exome sequencing: locating causative genes in rare disorders. Clin Genet. 2010 Jul;78(1):32-3.
Biesecker LG and Green RC. Diagnostic clinical genome and exome sequencing. N Engl J Med. 2014;370:2418-25.
ACMG Board of Directors. ACMG Policy Statement: Points to consider in the clinical application of genomic sequencing. Genet Med.
2012;14(8):759-76.
Farwell KD, et al. Enhanced utility of family-centered diagnostic exome sequencing with inheritance model-based analysis: results from
500 unselected families with undiagnosed genetic conditions. Genet Med. 2014 Nov 6. [Epub ahead of print]
Iglesias A, et al. The usefulness of whole-exome sequencing in routine clinical practice. Genet Med. 2014;16:922-931.