Coverage Policy Manual
Policy #: 2007011
Category: Laboratory
Initiated: July 2007
Last Review: December 2023
  Genetic Test: KIT (c-KIT, CD117)

Description:
CPT-4 manual coding instructions, in the header prior to the listing of Genetic Testing Code Modifiers: “This listing of modifiers is intended for reporting with molecular laboratory procedures related to genetic testing. Genetic testing modifiers should be used in conjunction with CPT and HCPCS codes to provide diagnostic granularity of service to enable providers to submit complete and precise genetic testing information without altering test descriptors. These two-character modifiers are categorized by mutation. The first (numeric) character indicates the disease category and the second (alpha) character denotes gene type. Introductory guidelines in the molecular diagnostic and molecular cytogenetic code sections of the CPT codebook provide further guidance in interpretation and application of genetic testing modifiers.”
 
These modifiers are appended to the molecular diagnostics codes 83890-83913 when molecular diagnostic procedures are performed to test for infectious disease, oncology, hematology, neurology, or inherited disorders to specify the probe type or condition tested. The new genetic modifiers may also be appended to the cytogenetic studies codes 88245-88291 when molecular diagnostic procedures are performed to test for oncologic or inherited disorders to specify the probe type or condition tested.
 
Genetic modifier ‘-0P’ is to identify testing for the c-kit receptor tyrosine kinase (KIT). The ability to molecularly classify individual cases of a specific disease that manifest different mutations of this gene allows for molecularly targeted therapy.

Policy/
Coverage:
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Genetic testing for determination of the presence or absence of the c-KIT gene or mutations thereof meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the diagnosis of:
 
      • acute lymphocytic leukemia,
      • chronic myelogenous leukemia,
      • gastrointestinal stromal tumor (GIST),
      • systemic mast cell disease, aggressive.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Molecular diagnostic testing for the c-KIT gene does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for, but not limited to, the following conditions: melanoma, dermatofibrosarcoma protuberans, hypereosinophilic syndrome, multiple myeloma, plasma cell leukemia, breast cancer, brain cancer, monoclonal gammopathy of unknown significance, retinoblastoma.
 
For members with contracts without primary coverage criteria, molecular diagnostic testing for the c-KIT gene is considered investigational for, but not limited to, the following conditions: melanoma, dermatofibrosarcoma protuberans, hypereosinophilic syndrome, multiple myeloma, plasma cell leukemia, breast cancer, brain cancer, monoclonal gammopathy of unknown significance, retinoblastoma. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Rationale:
2011 Update
A review of the literature has been conducted through December 2010.  There was no new literature identified that would prompt a change in the coverage statement.
  
Clinical Utility:
The clinical utility of a direct diagnostic genetic test for the determination of the presence or absence of the c-KIT gene or mutations thereof has been found to have little, if any, risks associated with it, and the benefits of this test can be invaluable in this selected population of patients.
 
New York State Validation Program:
Currently there is no evidence that any of the four laboratories, three of which are outside of the USA, currently performing genetic testing for the determination of the presence or absence or the c-KIT gene or mutations thereof have been validated by the New York State Validation program (Wadsworth).
 
Clinical Appropriateness:
Genetic testing for the determination of the presence or absence of the c-KIT gene or mutations thereof in applicable patients is deemed appropriate and necessary at this juncture.
 
EGAPP:
Genetic testing for the determination of the presence or absence of the c-KIT gene or mutations thereof has not been evaluated by EGAPP. It has been identified as a topic of interest, and it is currently on the list of tests to be evaluated in the future.
 
Gene Reviews:
Gene testing for the determination of the presence or absence of the c-KIT gene or mutations thereof has been evaluated by Gene Reviews, and currently, there is a full complement of information on this testing modality available on the Gene Reviews web site.
 
American College of Medical Genetics:
Gene testing for the determination of the presence or absence of the c-KIT gene or mutations thereof is not currently listed on the website of the American College of Medical Genetics.
 
Hayes Inc Assessment:
Hayes Inc. Assessment states that gene testing for determination of the presence or absence of the c-KIT gene or mutations thereof, has been evaluated and assessed, and it was concluded there is enough information available for a Technology Evaluation Assessment to be conducted. This will be done as soon as time allows in the future.
 
2012 Update
A literature search was conducted through May 2012.  There was no new literature identified that would prompt a change in the coverage statement.
 
2015 Update
A literature search conducted through May 2015 did not reveal any new information that would prompt a change in the coverage statement.  
 
2017 Update
A literature search conducted using the MEDLINE database through October 2017 did not reveal any new information that would prompt a change in the coverage statement.  
 
2018 Update
A literature search was conducted through November 2018.  There was no new information identified that would prompt a change in the coverage statement.  
 
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through November 2021. No new literature was identified that would prompt a change in the coverage statement.
 
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through November 2022. No new literature was identified that would prompt a change in the coverage statement.
 
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through November 2023. No new literature was identified that would prompt a change in the coverage statement.

CPT/HCPCS:
81272KIT (v kit Hardy Zuckerman 4 feline sarcoma viral oncogene homolog) (eg, gastrointestinal stromal tumor [GIST], acute myeloid leukemia, melanoma), gene analysis, targeted sequence analysis (eg, exons 8, 11, 13, 17, 18)
81273KIT (v kit Hardy Zuckerman 4 feline sarcoma viral oncogene homolog) (eg, mastocytosis), gene analysis, D816 variant(s)
81402Molecular pathology procedure, Level 3 (eg, >10 SNPs, 2-10 methylated variants, or 2-10 somatic variants [typically using non-sequencing target variant analysis], immunoglobulin and T-cell receptor gene rearrangements, duplication/deletion variants of 1 exon, loss of heterozygosity [LOH], uniparental disomy [UPD]) Chromosome 1p-/19q- (eg, glial tumors), deletion analysis Chromosome 18q- (eg, D18S55, D18S58, D18S61, D18S64, and D18S69) (eg, colon cancer), allelic imbalance assessment (ie, loss of heterozygosity) COL1A1/PDGFB (t(17;22)) (eg, dermatofibrosarcoma protuberans), translocation analysis, multiple breakpoints, qualitative, and quantitative, if performed CYP21A2 (cytochrome P450, family 21, subfamily A, polypeptide 2) (eg, congenital adrenal hyperplasia, 21-hydroxylase deficiency), common variants (eg, IVS2-13G, P30L, I172N, exon 6 mutation cluster [I235N, V236E, M238K], V281L, L307FfsX6, Q318X, R356W, P453S, G110VfsX21, 30-kb deletion variant) ESR1/PGR (receptor 1/progesterone receptor) ratio (eg, breast cancer) MEFV (Mediterranean fever) (eg, familial Mediterranean fever), common variants (eg, E148Q, P369S, F479L, M680I, I692del, M694V, M694I, K695R, V726A, A744S, R761H) TRD@ (T cell antigen receptor, delta) (eg, leukemia and lymphoma), gene rearrangement analysis, evaluation to detect abnormal clonal population Uniparental disomy (UPD) (eg, Russell-Silver syndrome, Prader-Willi/Angelman syndrome), short tandem repeat (STR) analysis
81404Molecular pathology procedure, Level 5 (eg, analysis of 2-5 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of 6-10 exons, or characterization of a dynamic mutation disorder/triplet repeat by Southern blot analysis) ACADS (acyl-CoA dehydrogenase, C-2 to C-3 short chain) (eg, short chain acyl-CoA dehydrogenase deficiency), targeted sequence analysis (eg, exons 5 and 6) AQP2 (aquaporin 2 [collecting duct]) (eg, nephrogenic diabetes insipidus), full gene sequence ARX (aristaless related homeobox) (eg, X-linked lissencephaly with ambiguous genitalia, X-linked mental retardation), full gene sequence AVPR2 (arginine vasopressin receptor 2) (eg, nephrogenic diabetes insipidus), full gene sequence BBS10 (Bardet-Biedl syndrome 10) (eg, Bardet-Biedl syndrome), full gene sequence BTD (biotinidase) (eg, biotinidase deficiency), full gene sequence C10orf2 (chromosome 10 open reading frame 2) (eg, mitochondrial DNA depletion syndrome), full gene sequence CAV3 (caveolin 3) (eg, CAV3-related distal myopathy, limb-girdle muscular dystrophy type 1C), full gene sequence CD40LG (CD40 ligand) (eg, X-linked hyper IgM syndrome), full gene sequence CDKN2A (cyclin-dependent kinase inhibitor 2A) (eg, CDKN2A-related cutaneous malignant melanoma, familial atypical mole-malignant melanoma syndrome), full gene sequence CLRN1 (clarin 1) (eg, Usher syndrome, type 3), full gene sequence COX6B1 (cytochrome c oxidase subunit VIb polypeptide 1) (eg, mitochondrial respiratory chain complex IV deficiency), full gene sequence CPT2 (carnitine palmitoyltransferase 2) (eg, carnitine palmitoyltransferase II deficiency), full gene sequence CRX (cone-rod homeobox) (eg, cone-rod dystrophy 2, Leber congenital amaurosis), full gene sequence CYP1B1 (cytochrome P450, family 1, subfamily B, polypeptide 1) (eg, primary congenital glaucoma), full gene sequence EGR2 (early growth response 2) (eg, Charcot-Marie-Tooth), full gene sequence EMD (emerin) (eg, Emery-Dreifuss muscular dystrophy), duplication/deletion analysis EPM2A (epilepsy, progressive myoclonus type 2A, Lafora disease [laforin]) (eg, progressive myoclonus epilepsy), full gene sequence FGF23 (fibroblast growth factor 23) (eg, hypophosphatemic rickets), full gene sequence FGFR2 (fibroblast growth factor receptor 2) (eg, craniosynostosis, Apert syndrome, Crouzon syndrome), targeted sequence analysis (eg, exons 8, 10) FGFR3 (fibroblast growth factor receptor 3) (eg, achondroplasia, hypochondroplasia), targeted sequence analysis (eg, exons 8, 11, 12, 13) FHL1 (four and a half LIM domains 1) (eg, Emery-Dreifuss muscular dystrophy), full gene sequence FKRP (fukutin related protein) (eg, congenital muscular dystrophy type 1C [MDC1C], limb-girdle muscular dystrophy [LGMD] type 2I), full gene sequence FOXG1 (forkhead box G1) (eg, Rett syndrome), full gene sequence FSHMD1A (facioscapulohumeral muscular dystrophy 1A) (eg, facioscapulohumeral muscular dystrophy), evaluation to detect abnormal (eg, deleted) alleles FSHMD1A (facioscapulohumeral muscular dystrophy 1A) (eg, facioscapulohumeral muscular dystrophy), characterization of haplotype(s) (ie, chromosome 4A and 4B haplotypes) GH1 (growth hormone 1) (eg, growth hormone deficiency), full gene sequence GP1BB (glycoprotein Ib [platelet], beta polypeptide) (eg, Bernard-Soulier syndrome type B), full gene sequence (For common deletion variants of alpha globin 1 and alpha globin 2 genes, use 81257) HNF1B (HNF1 homeobox B) (eg, maturity-onset diabetes of the young [MODY]), duplication/deletion analysis HRAS (v-Ha-ras Harvey rat sarcoma viral oncogene homolog) (eg, Costello syndrome), full gene sequence HSD3B2 (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2) (eg, 3-beta-hydroxysteroid dehydrogenase type II deficiency), full gene sequence HSD11B2 (hydroxysteroid [11-beta] dehydrogenase 2) (eg, mineralocorticoid excess syndrome), full gene sequence HSPB1 (heat shock 27kDa protein 1) (eg, Charcot-Marie-Tooth disease), full gene sequence INS (insulin) (eg, diabetes mellitus), full gene sequence KCNJ1 (potassium inwardly-rectifying channel, subfamily J, member 1) (eg, Bartter syndrome), full gene sequence KCNJ10 (potassium inwardly-rectifying channel, subfamily J, member 10) (eg, SeSAME syndrome, EAST syndrome, sensorineural hearing loss), full gene sequence LITAF (lipopolysaccharide-induced TNF factor) (eg, Charcot-Marie-Tooth), full gene sequence MEFV (Mediterranean fever) (eg, familial Mediterranean fever), full gene sequence MEN1 (multiple endocrine neoplasia I) (eg, multiple endocrine neoplasia type 1, Wermer syndrome), duplication/deletion analysis MMACHC (methylmalonic aciduria [cobalamin deficiency] cblC type, with homocystinuria) (eg, methylmalonic acidemia and homocystinuria), full gene sequence MPV17 (MpV17 mitochondrial inner membrane protein) (eg, mitochondrial DNA depletion syndrome), duplication/deletion analysis NDP (Norrie disease [pseudoglioma]) (eg, Norrie disease), full gene sequence NDUFA1 (NADH dehydrogenase [ubiquinone] 1 alpha subcomplex, 1, 7.5kDa) (eg, Leigh syndrome, mitochondrial complex I deficiency), full gene sequence NDUFAF2 (NADH dehydrogenase [ubiquinone] 1 alpha subcomplex, assembly factor 2) (eg, Leigh syndrome, mitochondrial complex I deficiency), full gene sequence NDUFS4 (NADH dehydrogenase [ubiquinone] Fe-S protein 4, 18kDa [NADH-coenzyme Q reductase]) (eg, Leigh syndrome, mitochondrial complex I deficiency), full gene sequence NIPA1 (non-imprinted in Prader-Willi/Angelman syndrome 1) (eg, spastic paraplegia), full gene sequence NLGN4X (neuroligin 4, X-linked) (eg, autism spectrum disorders), duplication/deletion analysis NPC2 (Niemann-Pick disease, type C2 [epididymal secretory protein E1]) (eg, Niemann-Pick disease type C2), full gene sequence NR0B1 (nuclear receptor subfamily 0, group B, member 1) (eg, congenital adrenal hypoplasia), full gene sequence PDX1 (pancreatic and duodenal homeobox 1) (eg, maturity-onset diabetes of the young [MODY]), full gene sequence PHOX2B (paired-like homeobox 2b) (eg, congenital central hypoventilation syndrome), full gene sequence PLP1 (proteolipid protein 1) (eg, Pelizaeus-Merzbacher disease, spastic paraplegia), duplication/deletion analysis PQBP1 (polyglutamine binding protein 1) (eg, Renpenning syndrome), duplication/deletion analysis PRNP (prion protein) (eg, genetic prion disease), full gene sequence PROP1 (PROP paired-like homeobox 1) (eg, combined pituitary hormone deficiency), full gene sequence PRPH2 (peripherin 2 [retinal degeneration, slow]) (eg, retinitis pigmentosa), full gene sequence PRSS1 (protease, serine, 1 [trypsin 1]) (eg, hereditary pancreatitis), full gene sequence RAF1 (v-raf-1 murine leukemia viral oncogene homolog 1) (eg, LEOPARD syndrome), targeted sequence analysis (eg, exons 7, 12, 14, 17) RET (ret proto-oncogene) (eg, multiple endocrine neoplasia, type 2B and familial medullary thyroid carcinoma), common variants (eg, M918T, 2647_2648delinsTT, A883F) RHO (rhodopsin) (eg, retinitis pigmentosa), full gene sequence RP1 (retinitis pigmentosa 1) (eg, retinitis pigmentosa), full gene sequence SCN1B (sodium channel, voltage-gated, type I, beta) (eg, Brugada syndrome), full gene sequence SCO2 (SCO cytochrome oxidase deficient homolog 2 [SCO1L]) (eg, mitochondrial respiratory chain complex IV deficiency), full gene sequence SDHC (succinate dehydrogenase complex, subunit C, integral membrane protein, 15kDa) (eg, hereditary paraganglioma-pheochromocytoma syndrome), duplication/deletion analysis SDHD (succinate dehydrogenase complex, subunit D, integral membrane protein) (eg, hereditary paraganglioma), full gene sequence SGCG (sarcoglycan, gamma [35kDa dystrophin-associated glycoprotein]) (eg, limb-girdle muscular dystrophy), duplication/deletion analysis SH2D1A (SH2 domain containing 1A) (eg, X-linked lymphoproliferative syndrome), full gene sequence SLC16A2 (solute carrier family 16, member 2 [thyroid hormone transporter]) (eg, specific thyroid hormone

References: Aslan DL, Oprea GM, et al.(2005) c-kit expression in adenoid cystic carcinoma does not have an impact on local or distant tumor recurrence. Head Neck, 2005; 27:1028-34.

Barry RJ, Moura LR, et al.(2007) Expression of C-kit in retinoblastoma: a potential therapeutic target. Br J Ophthalmol, 2007; [Epub ahead of print].

Biermann K, Klingmuller D, et al.(2006) Diagnostic value of markers M2A, OCT 3/4, AP-2gamma, PLAP and c-KIT in the detection of extragonadal seminomas. Histopathology, 2006; 49:290-7.

Droogendijk HJ, Kluin-Nelemans HJ, et al.(2006) Imatinib mesylate in the treatment of systemic mastocytosis: a phase II trial. Cancer, 2006; 107:345-51.

Haberier C, Geipi E, et al.(2006) Immunohistochemical analysis of platelet-derived growth factor receptor -alpha, -beta, c-kit, c-abi, and arg proteins in glioblastoma: possible implications for patient selection for imatinib mesylate therapy. J Neurooncol, 2006; 76:105-9.

Horny HP, Sotlar K, Valent P.(2007) Mastocytosis: state of the art. Pathobiology, 2007; 74:121-32.

Hungness SI, Akin C.(2007) Mastocytosis: advances in diagnosis and treatment. Curr Allergy Asthma Rep, 2007; 7:248-54.

Joensuu H, Puputti M, et al.(2005) Amplification of genes encoding KIT, PDGFRalpha and VEGFR2 receptor tyrosine kinases is frequent in glioblastoma multiforme. J Pathol, 2005; 207:224-31.

Pardanani A, Akin C, Valent P.(2006) Pathogenesis, clinical features, and treatment advances in mastocytosis. Best Pract Res Clin Haematol, 2006; 19:595-615.

Patnaik MM, Rindos M, et al.(2007) Systemic mastocytosis: a concise clinical and laboratory review. Arch Pathol Lab Med, 2007; 131:784-91.

Sihto H, Tynninen O, et al.(2007) Endothelial cell KIT expression in human tumours. J Pathol, 2007; 211:481-8.

Sorensen KB, Godballe C, et al.(2006) Parotid carcinoma: expression of kit protein and epidermal growth factor receptor. J Oral Pathol Med, 2006; 35:286-91.

Tefferi A, Pardanani A.(2004) Clinical, genetic, and therapeutic insights into systemic mast cell disease. Curr Opin Hematol, 2004; 11:58-64.

Wang-rodriguez J, Lopez JP, et al.(2006) STI-571 (Gleevec) potentiates the effect of cisplatin in inhibiting the proliferation of head and neck squamous cell carcinoma in vitro. Laryngoscope, 2006; 116:1409-16.

Went PT, Dirnhofer S, et al.(2004) Prevalence of KIT expression in human tumors. J Clin Oncol, 2004; 22:4514-22.

Wiseman SM, Masoudi H, et al.(2007) Anaplastic thyroid carcinoma: expression profile of targets for therapy offers new insights for disease treatment. Ann Surg Oncol, 2007; 14:719-29.


Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2024 American Medical Association.