Does Not Apply to Commercial Genetic Testing Program effective 6/1/2018
Whole exome sequencing (WES) analyses the portion of the genome that contains protein-coding DNA, known as exons; whole genome sequencing (WGS) analyses both coding and noncoding regions of the genome. WES and WGS have been proposed for use in children presenting with disorders and anomalies that have not been explained by standard clinical workup. While exons represent only about 2% of the genome, they account for approximately 85% of disease-causing genetic variants.
Genetic counseling is primarily aimed at individuals who are at risk for inherited disorders. Experts recommend formal genetic counseling when genetic testing for an inherited condition is considered.
Whole exome sequencing (WES) may be considered medically necessary if the medical appropriateness criteria are met (See Medical Appropriateness below).
Whole exome sequencing (WES) when used as a screening tool for asymptomatic individuals is considered investigational.
Whole genome sequencing (WGS) is considered investigational.
Pre- and post- genetic counseling as an adjunct to genetic testing is considered medically necessary.
Whole exome sequencing (WES) may be considered medically appropriate if ALL of the following are met:
Individual is 18 years of age or younger
There is potential for change in treatment or management of the individual being tested
Congenital anomalies and/or neurodevelopmental disorder(s) cannot be explained by standard non-invasive tests
Whole exome sequencing (WES) would be ANY ONE of the following:
Genetic etiology is the most likely explanation, even though no genetic testing has been done
A better alternative than standard invasive testing (e.g. muscle biopsy)
Previous genetic testing (e.g. targeted single gene testing, panel testing) has failed to yield a diagnosis
Any specific products referenced in this policy are just examples and are intended for illustrative purposes only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available. These examples are contained in the parenthetical e.g. statement.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
There are no regulations required by the U.S. Food and Drug Administration (FDA) for genetic testing. Laboratories performing clinical tests must be certified for high complexity testing under the Clinical Laboratory Improvement Amendments (CLIA) of 1988.
Published evidence of well-designed studies in peer review journals is insufficient to determine whether the use of whole genome sequencing tests improve health outcomes.
American College of Medical Genetics and Genomics. (2012). Policy statement. Points to consider in the clinical application of genomic sequencing. Retrieved May 14, 2013 from http://www.acmg.net.
American College of Medical Genetics and Genomics. (2014, September). ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencing. Retrieved June 29, 2017 from https://www.acmg.net.
American College of Medical Genetics and Genomics. (2017, February). Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. Retrieved June 29, 2017 from http://www.acmg.net.
BlueCross BlueShield Association. Medical Policy Reference Manual. (10:2017). Whole exome and whole genome sequencing for diagnosis of genetic disorders (2.04.102). Retrieved June 29, 2017 from BlueWeb. (33 articles and/or guidelines reviewed)
Monroe, G., Frederix, G., Savelberg, S., de Vries, T., Duran, K., van der Smagt, J., et. al., (2016, September) Effectiveness of whole-exome sequencing and costs of the traditional diagnostic trajectory in children with intellectual disability. Genetic Medicine. 18(9):949-56. Abstract retrieved July 5, 2017 from PubMed database.
Montenegro, G., Powell, E., Huang, J., Speziani, F., Edwards, Y., Beecham, G., et al. (2011). Exome sequencing allows for rapid gene identification in a Charcot-Marie-Tooth family. Annals of Neurology, 69 (3), 464-470. (Level 4 evidence)
Need, A. C., Shashi, V., Hitomi, Y., Schoch, K. V., McDonald, M. T., et al. (2012). Clinical application of exome sequencing in undiagnosed genetic conditions. Journal of Medical Genetics, 49 (6), 353-361. (Level 4 evidence)
Nguyen, M., and Charlebois, K. (2015, October) The clinical utility of whole-exome sequencing in the context of rare diseases - the changing tides of medical practice. Clinical Genetics. 88(4):313-9. Abstract retrieved July 5, 2017 from PubMed database.
Nolan, D., and Carlson, M. (2016, June) Whole exome sequencing in pediatric neurology patients: clinical implications and estimated cost analysis. Journal of Child Neurology. 31(7): 887-94. Abstract retrieved July 5, 2017 from PubMed database.
Rosell, A., Pena, L., Schoch, K., Spillmann, R., Sullivan, J., Hooper, S., et. al. (2016, October) Not the end of the odyssey: parental perceptions of whole exome sequencing (WES) in pediatric undiagnosed disorders. Journal of Genetic Counseling. 25(5):1019-31. Abstract retrieved July 5, 2017 from PubMed database.
Rump, P., Omid, J., van Dijk-Bos, K., Lennart, F., Johansson, A., van Essen, A., Verjeij, J., et. al., (2016) Whole-exome sequencing is a powerful approach for establishing the etiological diagnosis in patients with intellectual disability and microcephaly. BMC Medical Genomics. (2016)9:7. (Level 4 evidence)
Sener, E. F., Canatan, H., & Ozkul, Y. (2016). Recent advances in autism spectrum disorders: applications of whole exome sequencing technology. Psychiatry Investigation, 13 (3), 255-264. (Level 2 evidence)
Stark, Z., Tan, T., Chong, B., Brett, G., Yap, P., Walsh, M., et. al., (2016, November) A prospective evaluation of whole-exome sequencing as a first tier molecular test in infants with suspected monogenic disorders. Genetic Medicine. 18(1):1090-1096. Abstract retrieved July 5, 2017 from PubMed database.
Technology Evaluation Center. (2013, August). Special report: Exome sequencing for clinical diagnosis of patients with suspected genetic disorders (Vol. 28, No. 3). Chicago: BlueCross BlueShield Association. (61 articles and/or guidelines reviewed)
Thevenon, J., Duffourd, Y., Masurel-Paulet, A., Lefebvre, M., Feillet, F., El Chehadeh-Djebbar, S., et. al. (2016, June) Diagnostic odyssey in severe neurodevelopmental disorders: toward clinical whole-exome sequencing as a first-line diagnostic test. Clinical Genetics. 89(6):700-7. Abstract retrieved July 5, 2017 from PubMed database.
Winifred S. Hayes, Inc. Genetic Test Evaluation (GTE) Indication. (2016, September). Whole genome sequencing fin neonatal and pediatric patients. Retrieved June 29, 2017 from www.Hayesinc.com/subscribers. (27 articles and/or guidelines reviewed)
Winifred S. Hayes, Inc. Genetic Test Evaluation (GTE) Report. (2013, August; last update search August 2014). Whole exome sequencing for noncancer indications. Retrieved May 11, 2015 from www.Hayesinc.com/subscribers. (44 articles and/or guidelines reviewed)
Yu, Y., Wu, B. L., Wu, J., & Shen, Y. (2012). Exome and whole-genome sequencing as clinical tests: A transformative practice in molecular diagnostics. Clinical Chemistry, 58 (11), 1507-1509. (Level 2 evidence)
ORIGINAL EFFECTIVE DATE: 1/11/2014
MOST RECENT REVIEW DATE: 8/9/2018
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
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