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L.2.04.449
Genetic testing to determine kinesin-like protein 6 (KIF6) Trp719Arg variant status is being evaluated as a test to predict the risk of future cardiovascular events and as a test to predict response to statin therapy, particularly in high-risk patients. Kinesin-like protein 6 (KIF6) belongs to the kinesin superfamily of proteins involved in intracellular transport. The exact function of the KIF6 gene product is as yet undetermined. It has been reported that the gene is not expressed in the vasculature, the primary site of atherosclerosis, but is expressed in low levels in the brain, connective tissue, colon, eye, pharynx, skin, and testes. In contrast, a study presented at a 2010 American Heart Association scientific session reported on data derived from tissue immunohistochemistry, locating KIF6 protein in macrophages surrounding neovessels and in foam cells in human atherosclerotic lesions. Nevertheless, there is no strong evidence that KIF6 protein plays a direct biologic role in atherosclerosis, lipid metabolism, coronary artery disease (CAD), or myocardial infarction (MI).
Analysis of prospective observational studies of cardiovascular health and the placebo arm of randomized controlled trials of statin interventions in at risk populations have suggested a significant association between thearginine-to-tryptophan substitution at position 719 (Trp719Arg) single nucleotide variant (rs20455) in kinesin-like protein 6 (KIF6) and the development of clinical coronary artery disease (CAD). Approximately 60% of the population carries the putative KIF6 high-risk 719Arg allele. Moreover, carriers of the 719Arg allele in the treatment arms of the statin trials appeared to be at no increased or decreased risk of CAD or recurrent myocardial infarction, depending on the intensity of the statin therapy. These results supported the development of a KIF6 Trp719Arg genotyping test for use as a predictor of CAD risk and of the likely effectiveness of statin therapy.
Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests (LDTs) must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments (CLIA). Laboratories that offer LDTs must be licensed by the CLIA for high-complexity testing. To date, the U.S. Food and Drug Administration (FDA) has chosen not to require any regulatory review of this test.
In January 2011, Celera Corp. submitted a premarket approval application to the FDA for its KIF6 Genotyping Assay performed using Abbott's m2000™ instrument system. In April, the FDA informed Celera that its application was not approvable “without major amendment.” The data and publications submitted were deemed “...insufficient to demonstrate the safety and effectiveness of the device for its proposed intended use.” The FDA indicated that additional data on clinical utility might be required, which could include conducting a randomized controlled trial.
Now a wholly owned subsidiary of Quest Diagnostics, Celera holds a U.S. patent on methods of determining coronary heart disease risk through detection of the KIF6 gene variant and reduction of such increased risk by atorvastatin and pravastatin therapy and offers the Cardio IQ™ KIF6 Genotype.
KIF6 genotyping is considered investigational for predicting cardiovascular risk and/or the effectiveness of statin therapy.
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The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.
03/31/2011: Approved by Medical Policy Advisory Committee.
03/27/2012: Policy reviewed; no changes.
01/14/2013: Added the following new 2013 CPT codes to the Code Reference section: 81479.
03/14/2014: Policy reviewed; no changes to policy statement. Removed deleted CPT codes 83890-83894, 83896-83898, 83900-83909, and 83912 from the Code Reference section.
03/17/2015: Policy description updated with information regarding the KIF6 protein and tests. Policy statement unchanged.
07/30/2015: Code Reference section updated for ICD-10.
03/30/2016: Policy description updated regarding laboratory-developed tests. Policy statement unchanged. Policy guidelines updated to add genetic counseling information. Investigative definition updated.
06/06/2016: Policy number A.2.04.67 added.
06/22/2017: Policy description updated. Policy statement unchanged. Policy Guidelines updated regarding standard terminology for variant classification.
06/12/2018: Policy reviewed. Policy statement unchanged. Policy Guidelines updated regarding genetics nomenclature and genetic counseling.
06/05/2019: Policy reviewed; no changes.
07/13/2020: Policy reviewed. Policy statement unchanged. Policy Guidelines updated to remove genetics nomenclature and genetic counseling information.
08/27/2021: Policy reviewed; no changes.
11/16/2022: Policy updated to change the medical policy number from A.2.04.67 to L.2.04.449.
05/01/2023: Policy reviewed; no changes.
04/30/2024: Policy reviewed; no changes.
08/01/2025: Policy reviewed; no changes.
Blue Cross Blue Shield Association policy # 2.04.67
This may not be a comprehensive list of procedure codes applicable to this policy.
Code Number | Description |
CPT-4 | |
81479 | Unlisted molecular pathology procedure |
84999 | Unlisted chemistry procedure |
HCPCS | |
ICD-10 Procedure | |
ICD-10 Diagnosis |
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