Genetic Molecular Testing for Miscellaneous Indications*

Medical Policy: 02.04.08 
Original Effective Date: May 2005 
Reviewed: October 2011 
Revised: January 2012 

Benefit Application
Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.

Description: 

Genetic molecular testing involves the analysis of human DNA, RNA, chromosomes, certain metabolites and proteins to detect heritable disease-related genotypes, mutations, phenotypes, or karyotypes for clinical purposes. Certain genetic molecular tests have been demonstrated to be of significant value in providing information with regard to diagnosis and treatment of a given condition. However, clinical usefulness of any genetic molecular test is dependent on the availability of specific, effective interventions to reduce risk or treat disease. When the results of conventional tests are inconclusive, the use of genetic molecular testing may add an additional measure of certainty to diagnosis, permitting refinement of clinical therapy.

Commercial availability in and of itself does not ensure that a genetic molecular test is indicated for clinical application. Genetic molecular testing is a rapidly evolving science in which the significance of detecting specific germ-line mutations has yet to be clarified, especially in individuals with no known family history of a given disease.

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Prior Approval: 

Prior approval is recommended for genetic testing.  Submit a prior approval now.

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Policy: 

Certain genetic molecular tests may be considered medically necessary for patients with personal or family history features suggestive of a genetic susceptibility condition when: 

• the results of the test will assist in diagnosis

AND

• the results of the test will influence  at least one of the following
  • Medical or surgical management
  • Protective measures
  • Life-style adaptations 

All genetic molecular testing must be conducted in a laboratory certified, at a minimum, under the Clinical Laboratory Improvement Amendments of 1988 (CLIA).

All genetic molecular testing must be accompanied by pre- AND post-test genetic counseling with a physician or a licensed or certified genetic counselor, which discusses the possible risks and benefits of early detection and prevention modalities.

Cystic Fibrosis

Genetic molecular testing may be considered medically necessary for individuals presenting with symptoms of cystic fibrosis but have a negative sweat chloride test.

Long QT syndrome

Genetic molecular testing for the diagnosis and management of Long QT syndrome may be considered medically necessary for any of the following individuals:

• Those presenting with demonstrated prolonged QT-interval on resting EKG or Holter and in whom acquired cause has been ruled out
• Those with a positive first-degree family history of sudden death or near-sudden death
• Those with a first-, second-, or third-degree relative with a known LQTS mutation.
• Those with a first-, second-, or third-degree relative diagnosed with LQTS by clinical means whose genetic status is unavailable.
• Those with signs and/or symptoms indicating a moderate-to-high pretest probability of LQTS*

*Determining the pretest probability of LQTS is not standardized. AN example of a patient with a moderate-to-high pretest probability of LQTS is a patient with a Schwartz score of 2-3.

Hypertrophic Cardiomyopathy (HCM)

Genetic molecular testing may be considered medically necessary for the following individuals:

• Those with a firm clinical diagnosis of HCM to determine the causative mutation
• First-degree relatives of an individual in whom genetic testing has confirmed a pathogenetic mutation

Catecholaminergic polymorphic ventricular tachycardia (CPVT)

Genetic molecular testing may be considered medically necessary for the following individuals:

• Those in whom a cardiologist has established a clinical index of suspicion for CPVT based on examination of the patient’s clinical history, family history, and expressed electrocardiographic features during provocative stress testing with cycle, treadmill, or catecholamine infusion to determine the causative mutation
• First-degree relatives of an individual in whom genetic testing has confirmed a pathogenetic mutation
• In families with a known CPVT-associated mutation, confirmatory genetic testing may be performed at birth to allow prompt initiation of beta blocker therapy in mutation-positive subjects

Tay Sachs disease

Genetic molecular testing for the diagnosis and management of Tay Sachs disease may be considered medically necessary for any of the following individuals:

• Those with known risk factors (Ashkenazi Jewish or French-Canadian heritage, family history, medical history) for Tay Sachs disease
• For partners of Tay Sachs disease carriers as an aid in reproductive decision-making
• For prenatal diagnosis when both parents are known to be Tay Sachs disease carriers
• For individuals suspected of having a variant form of Tay Sachs disease, such as adult- or juvenile-onset or chronic Tay Sachs disease
• For individuals suspected of having a pseudodeficiency condition (asymptomatic non-Jewish individuals with low in vitro Hex-A activity).

Factor V Leiden thrombophilia

Genetic molecular testing may be considered medically necessary for the diagnosis and management of factor V Leiden thrombophilia for patients presenting with any of the following:

• Age ≤ 50, any history of unexplained venous thrombosis
• Age ≤ 50 with unexplained arterial thrombosis in the absence of other risk factors for atherosclerotic vascular disease
• Venous thrombosis in unusual sites such as portal hepatic, mesenteric, and cerebral veins
• Recurrent venous thrombosis
• Venous thrombosis and a strong family history of thrombotic disease
• Venous thrombosis in pregnant women or women taking oral contraceptives
• Asymptomatic first-degree relatives of individuals with proven symptomatic thrombophilia
• Myocardial infarction in female smokers under age 50
• Recurrent pregnancy loss (i.e., two or more consecutive pregnancy losses)

FMR1 gene analysis (Fragile X syndrome; Martin-Bell syndrome; Marker X syndrome)

Genetic molecular testing may be considered medically necessary for the diagnosis and management of patients exhibiting signs and symptoms suggestive of Fragile X syndrome. Behavior problems associated with Fragile X syndrome include (not exhaustive list):

• Delay in crawling, walking, or twisting
• Hand clapping or hand biting
• Hyperactive or impulsive behavior
• Mental retardation
• Speech and language delay
• Tendency to avoid eye contact

Physical signs may include (not exhaustive list):

• Flat feet
• Flexible joints and low muscle tone
• Large body size
• Large forehead or ears with prominent jaw
• Long face
• Soft skin

Some of these signs and symptoms are present at birth, while others may not develop until after puberty.

Genetic molecular testing undertaken for the purpose of obtaining information, and when no course of treatment or prevention is anticipated, is considered not medically necessary.

Genetic molecular tests directly marketed and made available to the consumer are considered not medically necessary. 

Conditions or circumstances for which genetic molecular testing is considered not medically necessary include, but are not limited to:

• Alzheimer’s disease
• Alpha 1-antitrypsin deficiency
• ataxia telangiectasia syndrome
• hemophilia A and B
• Huntington’s chorea
• myotonic dystrophy
• sickle cell disease
• Prader-Willi syndrome
• amyotrophic lateral sclerosis
• Left ventricular noncompaction cardiomyopathy (LVNC)
• Assessment of risk for cardiovascular disease in the general population, specifically heart disease and stroke

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Procedure Codes and Billing Guidelines: 

• To report provider services, use appropriate CPT* codes, Modifiers Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or ICD-9-CM diagnostic codes.

These HCPCS codes may be used to report genetic testing:

• S3800 Genetic testing for amyotrophic lateral sclerosis (ALS)
• S3835 Complete gene sequence analysis for cystic fibrous genetic testing
• S3837 Complete gene sequence analysis for hemochromatosis genetic testing
• S3842 Genetic testing for Von Hippel-Lindau disease
• S3843 DNA analysis of the F5 gene for susceptibility to factor V Leiden thrombophilia
• S3844 DNA analysis of the connexin 26 gene (GJB2) for susceptibility to congenital, profound deafness
• S3845 Genetic testing for alpha-thalassemia
• S3846 Genetic testing for hemoglobin E beta-thalassemia testing
• S3847 Genetic testing for Tay-Sachs disease
• S3848 Genetic testing for Gaucher disease
• S3849 Genetic testing for Niemann-Pick disease
• S3850 Genetic testing for sickle cell anemia
• S3851 Genetic testing for Canavan disease
• S3852 DNA analysis for APOE epilson 4 allele for susceptibility to Alzheimer's disease
• S3853 Genetic testing for myotonic muscular dystrophy
• S3855 Genetic testing for detection of mutations in the presenilin, 1 gene
• S3860 Genetic testing, comprehensive cardiac ion channel analysis, for variants in 5 major cardiac ion channel genes for individuals with high index of suspicion for familial long QT syndrome (LQTS) or related syndromes
• S3861 Genetic testing, sodium channel, voltage-gated, type V, alpha subunit (SCN5A) and variants for suspected Brugada Syndrome
• S3862 Genetic testing, family-specific ion channel analysis, for blood-relatives of individuals (index case) who have previously tested positive for a genetic variant of a cardiac ion channel syndrome using either one of the above test configurations or confirmed results from another laboratory
• 88248 Chromosome analysis for breakage syndromes; baseline breakage, score 50-100 cells, count 20 cells, 2 karyotypes (eg, for ataxia telangiectasia, Fanconi anemia, fragile X)    

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Selected References: 

• Burke W. Genetic testing. N Engl J Med; 2002 Dec; 347(23): 1867-75.
• Mathew C. Post genomic technologies: hunting the genes for common disorders. BMJ 2001; 322:1031-4.
• GeneTests-GeneReviews web site; http//www.geneclinics.org
• McConnell LM, Koenig BA, Greely HT et al. Genetic testing and Alzheimer’s disease: has the time come? Alzheimer Disease Working Group of the Stanford Program in genomics, Ethics & Society. Nat Med 1998; 4(7):757-9.
• Tsunag D, Larson EB, Bowen J et al. The utility of apolipoprotein E genotyping in the diagnosis of Alzheimer disease in a community-based case series. Arch Neurol 1999; 56(12):1489-95.
• Guttmacher AE, Collins FS. Genomic Medicine-a primer. N Engl J Med; 2002 347(23):1512-20.
• OMIM: Online Mendelian Inheritance in Man. Bethesda, Md.: National Center for Biotechnology Information. Accessed February 15, 2005, at http://www.ncbi.nlm.nih.gov/omim/.
• Ashley-Koch A, Yang Q, Olney RS. Sickle hemoglobin (HbS) allele and sickle cell disease a HuGE review. Am J Epidemiol 2000; 151:839-45.
• Califf RM. Defining the Balance of Risk and Benefit in the Era of Genomics and Proteomics. Health Affairs Jan-Feb 2004; 23(1):77-87.
• Institute for Clinical Systems Improvement (ICSI). Genetic Carrier Testing for Cystic Fibrosis. Technology Assessment Report. TA#69. Copyright© 2003 by ICSI.
• Philips KA, Ackeran MJ, Sakowski J. Cost effectiveness analysis of genetic testing for familial Long QT syndrome in symptomatic index cases. Heart Rhythm. 2005; 1294-300.
• American College of Obstetrics and Gynecology (ACOG) Committee on Genetics. Opinion #318: Screening for Tay Sachs disease. Obstet Gynecol. 2005; 106:893-4.
• Marchiori A, Mosena L, Prins MH et al. The risk of recurrent venous thromboembolism among heterozygous carriers of factor V Leiden or prothrombin G20210A mutation. A systematic review of prospective studies. Haematologica. 2007 Aug;92(8):1107-14.
• Wu O, Robertson L, Ttwaddle S et al. Screening for thrombophilia in high-risk situations: systematic review and cost-effectiveness analysis. The Thrombosis: risk and Economic Assessment of Thrombophilia Screening (TREATS) study. Health Technol Assess. 2006 Apr;10(11):1-110.
• Hershberger RE, Lindenfeld J, Mestroni L et al. Genetic evaluation of cardiomyopathy- A Heart Failure Society of America Practice Guideline. J Cardiac Fail 2009;15:83-97.
• Ackerman MJ, Priori SG, Willems S et al. HRS/EHRA Expert Consensus Statement on the State of Genetic Testing for the Channelopathies and Cardiomyopathies. Europace. 2011 Aug;13(8):1077-1099.
• Goldman JS, Hahn SE, Williamson J et al. Genetic counseling and testing for Alzheimer disease: Joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genet Med. 2011 Jun;13(6):597-605.
• Berg AO. Recommendations from the EGAPP Working Group: Genomic profiling to assess cardiovascular risk to improve cardiovascular health. Genet Med 2010 Dec;12(12):839-43.
• Albert CM, MacRae CA, Chasman DI et al. Common variants in cardiac ion channel genes are associated with sudden cardiac death. Circ Arrhythm Electrophysiol 20110; 3(3):222-9.
• Migdalovich D, Moss AJ, Lopes CM et al. Mutation and gender specific risk in type-2 long QT syndrome: Implications for risk stratification for life-threatening cardiac events in patients with long QT syndrome. Heart Rhythm 2011; March 24 [Epub ahead of print]. 

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Policy History: 

Date                                        Reason                               Action

November 2010                    Interim review                     Policy revised

October 2011                       Annual review                     Policy revised

January 2012                        Interim review                     Policy revised

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Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

*Current Procedural Terminology © 2010 American Medical Association. All Rights Reserved.