Approved Gene Testing (M00041, V14)

MolDX

Approved Gene Testing (M00041, V14)

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After a review of the current available literature, the MolDX Program has determined that testing for the following genes/gene components meets the Medicare criteria for a covered service. This listing has been updated with 2016 CPT codes.

#	CPT Code	Description
1.	81170	ABL1, ga
2.	81206	BCR_ABL1, majbp qual quant (p210)
3.	81207	BCR_ABL1, minbp qual quant (p190)
4.	81208	BCR_ABL1, other bp qual quant
5.	81210	BRAF, V600E
6.	81211	BRCA1, BRCA2, fgs cdup_del
7.	81217	BRCA2, kfv
8.	81218	CEBPA, fgs
9.	81225	CYP2C19, cv
10.	81226	CYP2D6, cv
11.	81235	EGFR, cv
12.	81245	FLT3, ITD
13.	81246	FLT3, TKD
14.	81256	HFE, cv
15.	81261	IGH, amp
16.	81262	IGH, dp
17.	81263	IGH, var reg
18.	81264	IGK, gr
19.	81265	STR
20.	81266	STR add  (for transplants)
21.	81267	Chimerism, no cell
22.	81268	Chimerism, with cell
23.	81270	JAK2, V617F
24.	81272	KIT, tsa
25.	81273	KIT,  D816
26.	81275	KRAS, codons 12 and 13
27.	81275	KRAS, exon 1
28.	81276	KRAS, addvar
29.	81287	MGMT, ma
30.	81288	MLH1, ma
31.	81292	MLH1, fgs
32.	81293	MLH1, kfv
33.	81294	MLH1, dup_del
34.	81295	MSH2, fgs
35.	81296	MSH2, kfv
36.	81297	MSH2, dup_del
37.	81298	MSH6, fgs
38.	81299	MSH6, kfv
39.	81300	MSH6, dup_del
40.	81301	MSI
41.	81310	NPM1, exon 12
42.	81311	NRAS, ex 2-3
43.	81313	PCA3
44.	81314	PDGFRA, tsa
45.	81315	PML_RAR, cbp
46.	81316	PML_RAR, sbp
47.	81317	PMS2, fgs
48.	81318	PMS2, kfv
49.	81319	PMS2, dup_del
50.	81321	PTEN, fgs
51.	81322	PTEN, kfv
52.	81323	PTEN, dup_del
53.	81332	SERPINA, cv
54.	81340	TRB, beta
55.	81341	TRB, dp
56.	81342	TRG, gamma
57.	81370	HLA I-II, lr ant
58.	81371	HLA I-II, lr verification
59.	81372	HLA I, lr complete
60.	81373	HLA I, lr locus ea
61.	81374	HLA I, lr 1 ant.
62.	81375	HLA II, lr DRB1/3/4/5, DQB1
63.	81376	HLA II, lr locus ea
64.	81377	HLA II, lr antigen ea
65.	81378	HLA I-II, hr A, B, C, DRB1
66.	81379	HLA I, hr complete
67.	81380	HLA I, hr locus ea
68.	81381	HLA I, hr allele ea
69.	81382	HLA II, hr locus ea
70.	81383	HLA II, hr allele ea
71.	81400	ACE, idv
72.	81400	F13B, V34L
73.	81400	F2, 1199G>A
74.	81400	F5, HR2
75.	81400	F7, R353Q
76.	81400	FGB, -455G>A
77.	81400	HPA, panel
78.	81400	HPA-1
79.	81400	HPA-2
80.	81400	HPA-3
81.	81400	HPA-4
82.	81400	HPA-5
83.	81400	HPA-15
84.	81400	IL28B, rs12979860
85.	81400	SERPINE1, 4G
86.	81401	ABL1, T315I
87.	81401	CBFB_MYH11, cv
88.	81401	CCND1_IGH, ta majbp qual qual
89.	81401	E2A_PBX1, ta qual quan,
90.	81401	EML4_ALK, ta
91.	81401	ETV6_RUNX1, ta qual quan
92.	81401	EWSR1_ERG, ta qual quan
93.	81401	EWSR1_FLI1, ta qual quan
94.	81401	EWSR1_WT1, ta qual quan
95.	81401	F11, cv
96.	81401	FIP1L1_PDGFR, qual quan
97.	81401	FOXO1_PAX3, ta, qual quan
98.	81401	FOXO1_PAX7, ta, qual quan
99.	81401	IGH/BCL2, sbp
100.	81401	MUTYH, cv
101.	81401	PAX8_PPARG, ta
102.	81401	RUNX1_RUNX1T1, ta qual quan
103.	81401	TPMT, cv
104.	81401	TYMS
105.	81401	VWF, cv
106.	81402	IGH_BCL2, majbpr_mcrbp qul_qun
107.	81402	KIT, cv
108.	81403	EPCAM, kfv
109.	81403	F8, intron 1 and 22a
110.	81403	HEA, gs
111.	81403	IDH1, exon 4
112.	81403	IDH1_ IDH2, exon 4 panel
113.	81403	IDH2, exon 4
114.	81403	JAK2, exon 12 and 13
115.	81403	MUTYH, kfv
116.	81403
117.	81403	RET, kfv
118.	81403	VHL, dup_del
119.	81403	VWF, tsa 2A, 2B, 2M
120.	81404	CDKN2A, fgs
121.	81404	NRAS, exon 1, 2
122.	81404	PRSS1, fgs
123.	81404	RET, cv
124.	81404	VHL, fgs
125.	81405	MEN1, fgs
126.	81405	RET, tsa
127.	81405	VWF, tsa 2N
128.	81406	RET, fgs
129.	81445	Tsa panel, solid organ neoplasm, 5-50 genes
130.	81450	Tsa panel, hematolymphoid neoplasm, 5-50 genes
131.	81455	Tsa panel, solid organ or hematolymphoid neoplasm,  51 or >
132.	81479	ALK
133.	81479	BCR_ABL1, 210 + 190
134.	81479	BCR_ABL1, 210 + 190 +other
135.		CALR_MPL
136.	81479	CYP2D6, CYP2C19
137.	81479	ERBB2
138.	81479	ERCC1
139.	81479	FLT3, ITD + TKD
140.	81479	HER2
141.	81479	IGH, IGK
142.	81479	MYD88, L265P
143.	81479	NRAS, 2,3,4
144.	81479	RET/PTC
145.	81479	ROS1
146.	81479	TRB/TRG

The following tests have completed the MolDX Technical Assessment Process and limited coverage has been established. Please review the companion policy and/or article for test specific information.

#	Proprietary Test Name	Manufacturer	Effective Date	CPT	MCD #	MolDX Article #
1.	Afirma	Veracyte	1/1/2012	81545	A523098	M00015
2.	Allomap	XDx	2/28/2012	81595	A53099	M00016
3.	Avise PG	Exagen Diagnostics	5/1/2012	84999	A53100	M00026
4.	BRACAnalysis® Rearrangement Test (BART)	Myriad Genetics	12/1/2006	81213	L36082
5.	BRCA1 Analysis	Myriad Genetics	12/1/2006	81214	L36082
6.	BRCA1/2	Ambry	3/1/2014	81162	L36082
7.	BRACAnalysis CDx	Myriad Genetics	12/19/14	81162	L36082	M00120
8.	BRCAssureSM	LabCorp	3/1/2014	81162	L36082
9.	BRCAvantage, Comprehensive	Quest	3/1/2014	81162	L36082
10.	Breast Cancer Index	BioTheranostics	11/4/2014	81479	L35631
11.	Cancer26	MUSC	10/3/2013	81445	NA
12.	CellSearch	Veridex	5/1/2012	86152 OR 86153	L35071
13.	cobas BRAF	Roche	9/7/2012	81210-22	A54018	M00111
14.	cobas EGFR	Roche	9/5/2013	81235-22	A54021	M00110
15.	cobas KRAS	Roche	5/7/2015	81275-22	A54472	M00121
16.	Comprehensive BRACAnalysis®	Myriad Genetics	12/1/2006	81211	L36082
17.	Confirm MDx	MDx Health	11/4/2014	81479	L35632
18.	Corus CAD	CardioDx	7/30/2012	81493	A53102	M00009
19.	CTID	BioTheranostics	12/27/2011	81540	A53101	M00027
20.	Decipher	GenomeDX	10/01/2015	81479	L35868
21.	FoundationOne®	Foundation One	10/01/2015	81479	L36143
22.	GeneSight	Assurex Health	10/27/2014	81479	L35633
23.	HERmark	LabCorp	12/9/2011	81479	A53103	M00028
24.	Integrated BRAC Analysis ®	Myriad Genetics	12/1/2006	81479	L36082
25.	Mammaprint	Agendia	11/16/2009	81479	A53104	M00029
26.	OncotoypeDx Colon	Genomic Health	9/27/2011	81525	A53106	M00002
27.	OncotypeDX Breast	Genomic Health	3/26/2012	81479	A53105	M00003
28.	PreciseType™ HEA Bead	Immucor	6/22/2015	81403	L36074
29.	Progensa	Gen Probe	9/6/2012	81313	A53107	M00013
30.	Prolaris	Myriad Genetics	3/2/15	81479	L35869
31.	therascreen EGFR	Qiagen	9/5/2013	81235-22	A54021	M00110
32.	therascreen-Kras	Qiagen	4/30/2013	81275-22	A54472	M00121
33.	ThxID™ BRAF V600E/K Test	bioMerieux, Inc.	1/9/2014	81210-22	A54018	M00111
34.	Tissue of Origin	ResponseDx	12/22/2011	81504	A53108	M00034
35.	TRofile DNA	LabCorp	5/5/2012	87999
36.	Trofile	LabCorp	5/15/2012	87999	A53528	M00042
37.	Ventana ALK Assay	Roche	6/12/15	88342	A54656	M00122
38.	Vectra-DA	Crescendo	6/30/2012	81490	A53110	M00031
39.	Vysis	Abbott	10/2/2012	88374 OR 88377	A54656	M00122

Next Generation Sequencing Coding and Billing Guidelines (M00127, V1)

As published December 16, 2015.

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MolDX

Next Generation Sequencing Coding and Billing Guidelines (M00127, V1)

Next Generation Sequencing (NGS)
NGS testing platforms allow identification of somatic and/or germline alterations in multiple genes at the same time. This guideline focuses on two main types of somatic, tumor tissue-based, testing panels.  Germline panels will be addressed in another article as needed.

Targeted (aka Hot Spot) Tumor Panels
Targeted NGS panels identify somatic alterations known to occur in certain areas (i.e., 'hotspots') in specific genes of interest. Generally, these NGS panels can detect single nucleotide variants (SNVs or point mutations) and small (typically ≤10 bp) insertions or deletions. These alterations typically represent genomic targets with corresponding targeted cancer therapies. Identification of a genomic target guides use of the corresponding targeted therapy.

To bill for targeted NGS services, select CPT codes 81445, 81450 and 81455 according to the number of genes in your laboratory’s NGS panel for solid tumor and hematolymphoid neoplasms. The UOS for the NGS panel is one.

Note: Individual gene tests performed in the NGS panel should NOT be registered and reported with multiple CPT Tier 1 and/or Tier II codes. 

Comprehensive Genomic Profile (CGP) TestingCGP refers to NGS-based testing that has been optimized to identify all types of molecular alterations (i.e., SNVs, small and large insertions and deletions, CNVs, and rearrangements/translocations/fusions) in cancer-related genes in a single test using complex proprietary bioinformatics. 

Because CGP includes SNVs, small (≤ 10 bp) and large (> 10 bp) insertions and deletions, CNVs, AND rearrangements (i.e., translocations/fusions), CPT codes 81445, 81450, and 81455 do NOT describe a CGP service. Therefore, to report a CGP service, test providers should use CPT code 81479 - Unlisted molecular pathology procedure.

last updated on 12/16/2015

MolDX Response to Comments on CYP Testing

https://www.cms.gov/medicare-coverage-database/details/article-details.aspx?articleId=54236&ver=3&ContrId=353&ContrVer=1&LCDId=36311&name=353*1&UpdatePeriod=654&IsPopup=y&

Article ID 54236


Response to Comments

COMMENT	RESPONSE
Cover CYP2C19 for Clopidogrel on a case by case basis; all Clopidogrel treated patients after acute myocardial infarct; expand coverage to patients with high risk characteristics. We request that the LCD recognize individual medical review to allow coverage for CYP2C19 testing in the patient on clopidogrel who would be considered high risk based on clinical characteristics.	From the latest CPIC statement on CYP2C19 and CLOPIDOGREL (Scott, 2013), “Current data do not support the use of CYP2C19 genotype data to guide treatment in other scenarios”.
Cover CYP2C19 for Amitriptyline We recommend coverage of CYP2C19 testing for use in patients being treated with amitriptyline, nortriptyline, and the tricyclic anti-depressants.	While the literature is promising and it is likely that CYP-based drug dosing will eventually become the standard of care, the evidence does not yet support that drug selection or dosing based on CYP genotype improves patient outcomes outside of the scenarios described in the Covered Indications section of the LCD. We agree that CPIC guidelines are useful in evaluating the strength of clinically relevant pharmacogenetic data and attempt to incorporate these recommendations when evidence is strong and shows a significant clinical impact. CPIC classified the level of evidence to support an initial dose reduction for CYP2C19 poor metabolizers as moderate based on a lack of randomized trials. Further studies of amitriptyline, nortriptyline, and other TCAs are necessary to strengthen the robustness of this recommendation.
Cover CYP2C19 for Proton Pump Inhibitors We recommend coverage for CYP2C19 testing in conjunction with initiating therapy with omeprazole, lansoprazole, pantoprazole, or esomeprazole at standard dosing as first line therapy unless other evidence is submitted; we request for expansion of coverage to patients being treated with a PPI for GERD and H. Pylori.	We agree that the medical literature supports an association between CYP2C19 genotype and response to PPIs; however, the lack of risk of adverse effects and the simple recommendation to increase the dose in patients who do not respond does not support clinical utility for this testing at this time.
Cover CYP2D6 and/or CYP2C19 for Antidepressants for numerous diagnoses Multiple commenters recommended coverage of CYP2D6 testing for all TCAs and for all FDA-labeled indications and off-label indications accepted as medical practice and covered by Medicare, e.g. use of amitriptyline for treatment of neuropathic pain.	Although tricyclic antidepressants have similar pharmacokinetic properties, there is limited data regarding CYP2D6 genotyping and other TCAs. Evidence to support the use of genetic testing prior to initiating certain TCA due to the effects of genotype on drug efficacy and safety was reviewed and covered in this policy. However, there is insufficient evidence for CYP2D6 genotyping for individuals considering antipsychotic medications or other antidepressants. While the literature is promising and it is likely that CYP-based drug dosing will eventually become the standard of care, the evidence does not yet support that drug selection or dosing based on CYP genotype improves patient outcomes outside of the scenarios described in the Covered Indications section of the LCD. We agree that CPIC guidelines are useful in evaluating the strength of clinically relevant pharmacogenetic data and attempt to incorporate these recommendations when evidence is strong and shows a significant clinical impact. CPIC classified the level of evidence to support an initial dose reduction for CYP2C19 poor metabolizers as moderate based on a lack of randomized trials. Further studies of amitriptyline, nortriptyline, and other TCAs are necessary to strengthen the robustness of this recommendation.
Cover CYP2D6 for Codeine A commenter requested that the required level of evidence be applied uniformly, e.g. the strength of evidence for CYP2D6 for codeine is the same in the CPIC guidelines as that for CYP2C19 for clopidogrel and CYP2D6 for amitriptyline/ nortriptyline, which Noridian has determined have a sufficient level of evidence to cover. A commenter requested that Medicare provide coverage for medically necessary testing for ALL beneficiaries, regardless of age or reason for eligibility for Medicare, e.g. disability and that coverage for CYP2D6 genotyping for codeine (and related drugs) based on presence of national guidelines, the strength of evidence cited in the guidelines and the presence of an FDA black box warning.	The efficacy and toxicity, including severe or life-threatening toxicity after normal doses of codeine has been linked to an individual’s CYP2D6 genotype (Crews 2014). However, FDA warnings related to the highest risk patients (breastfed neonates and children) recommend against the use of codeine regardless of CYP2D6 genotype. CYP2D6 genotyping patients would indicate avoidance of codeine due to risk of adverse events in only 1-2% of the population, and there is considerable variation in the degree of severity of adverse events, with most not classified as serious. Codeine has been widely used without genotyping and is universally available so access to medical care is not limited. There is insufficient evidence to support clinical utility of genotyping for management of codeine therapy.
Coverage of CYP2C9 and VKORC1 according to NCD 90.1 Both CYP2C9 and VKOCR1 should be covered within the context of a clinical study/coverage with evidence development according to NCD 90.1; if significant reductions in hospitalizations have been conclusively proven through CYP2C9 and VKORC1 genotyping, why does the draft policy limit testing to patients who are “enrolled in a prospective, randomized, controlled study when the study meets the following standards	Noridian covers CYP2C9 and VKORC1 genotyping for warfarin as described under NCD 90.1. All other uses not specifically listed in the NCD or this LCD are considered experimental, investigational, and unproven. If Noridian has missed publications that clearly demonstrates reductions in hospitalizations, the commenter needs to provide this information via a reconsideration request.
Delay postponement of this LCD until 2016; delay implementation until further evidence confirming or negating the clinical utility of pharmacogenetic (PGx) testing is collected; advancements in medicine will be hindered without continued reimbursement for PGx testing; restricting coverage will greatly reduce availability of test data in coming years and considerably delay test inclusion in standard of care practices; LCD is clearly a cost control measure because it excludes all but a narrow subset of the conditions and providers that currently benefit for the testing; delay LCD so that the evidence regarding the true impacts of this decision can be thoroughly reviewed, analyzed and understood Commenters requested postponement of this LCD until additional data was forthcoming.	Noridian will reconsider published evidence when it becomes available. Coverage requires evidence of demonstrated clinical utility – that a test result improves patient outcomes, and/or changes physician management that improves patient outcomes. Clinical utility has only been established for a narrow subset of conditions. Evidence of improved patient outcomes will quickly establish standard of care.
Cover ICD-9 995.2 (Other and unspecified adverse effect of drug, medicinal and biologic substance), beneficiaries accepted into approved studies or participating in Medicare Innovations Programs (CPCI or Shared Savings), and for patients at high risk of gene-based adverse drug events. A commenter requested coverage for the above groups for the above patient groups if the LCD is implemented prior to 2016.	There is no published evidence to support coverage for CYP testing for the above patient groups.
Reconsider coverage of cytochrome P450 gene metabolizer status in relation to limited coverage for GeneSight Psychotropic Panel.Noridian should reconsider their current position on the utility of individual cytochrome P450 gene metabolizer status in relation to limited coverage provided for Genesight® Psychotropic Panel.	GeneSight is multiplex pharmacogenomic test involving the analysis of fifty alleles (SNPs) from six different genes and a clinical outcomes-based decision support modeling tool that weights the influence of the various alleles/SNPs with respect to thirty-two different psychotropic pharmaceutical agents. The test results in the differentiation of psychoactive drugs that are likely to be effective and well-tolerated by a particular patient versus those that are not. In multiple prospective clinical studies, the use of GeneSight® to guide neuropsychiatric pharmaceutical selection and prescription has demonstrated an increased patient response to treatment from 60% to 250% (as measured by the standardized 17-item Hamilton Rating Scale for Depression or HAM-17; response is defined as = 50% reduction in HAM-D17 score) versus unguided, empirical treatment (or treatment as usual). Prospective evidence is required to demonstrate the effectiveness and utility for individual or P450 gene combination testing.
LCD is inconsistent with expert panel recommendations The Noridian Proposal is inconsistent with expert panel recommendations that were based on evaluation of the scientific literature that was used to develop drug-gene specific guidelines.	Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. They are not binding and intended only to assist clinicians in decision making.
The FDA has issued Black Box Warnings for over 100 medications recommending pharmacogenomic markers need to be assessed before and if patients are placed on these medications.	There is clear evidence of the clinical validity of CYP450 genotyping. However, there is limited evidence that genotyping and subsequent alterations to patient management improve patient outcomes for many scenarios; the clinical utility of CYP450 genotyping is proven in limited scenarios only. The draft LCD does not conflict with the FDA’s assessment of the clinical validity of CYP450 genotyping and potential relationship between genotype and drug response. FDA labeling as referenced does not mandate genotyping, but rather serves to warn clinicians that certain patient subgroups may exhibit altered drug response, and clinicians should be aware of alternative treatment strategies when appropriate. The draft LCD defines clinical scenarios where genotyping improves patient outcomes compared to outcomes when genotyping is not performed, which is not addressed by the FDA.
Who and what establishes “insufficient” data? Exactly who and what defines the term “insufficient” data to support coverage of any and all CYP450 and VKORC1 genetic mutation tests utilized in the practice of medicine; if significant reductions in hospitalizations have been conclusively proven through CYP2C9 and VKORC1 genotyping,	For Medicare coverage purposes, Medicare Administrative Contractor (MAC) Medical Directors establish sufficiency of data. A well characterized hierarchy of evidence is recognized by trained clinicians and scientists. In the absence of published scientific evidence that demonstrates clinical utility, the data is “insufficient”.