MP-11 Genetic Testing for Non-Cancerous Diseases Form
Medical Policy Genetic Testing for Non-Cancerous Disease
Review/Revision Date: 04/26/2022Page 1 of 15
Genetic Testing for Non-Cancerous Disease Policy Number: MP-11 Current Effective Date: 04/26/2022 Original Effective Date: 01/01/2016 Next Review/Revision Date: 04/26/2024 Plans: QUEST Integration (Medicaid) & AlohaCare Advantage Plus (SNP Medicare)
Purpose 1.1 The purpose of this policy is to define the medical necessity framework for genetic testing for non- cancerous diseases. Because of the rapidity with which the field of genetic testing is evolving, medical policies cannot address every genetic test available. AlohaCare has specific medical policies for genetic tests which are established and have proven utility. Please see the specific AlohaCare policy for those genetic tests. If a genetic test is requested which is not addressed in an AlohaCare policy, this policy describes the medical necessity criteria for coverage.
Policy 2.1 As science advances, genetic testing has become more common. However, most genetic tests are not regulated, meaning there is no independent analysis to verify the accuracy of the test or the claims of the lab performing the test. Accurate diagnosis could be the most critical aspect of healthcare.
2.2 As a result of the current limited oversight, genetic tests have been introduced before they have been demonstrated to be safe, effective, and useful. There is laboratory variability in standards, variant classification, and staff training; and there is a lack of sufficient information in product briefs and guides to properly inform or educate providers and patients. With this information gap, objective (non-industry sponsored) peer-reviewed medical literature becomes critical in determining if a test is medically necessary when Federal and State agencies do not provide guidance.
• Definitions o Adult-Onset Disease – disorders or diseases that normally become symptomatic in adult life. o Analytic Validity – the technical accuracy of a test in detecting a gene variant that is present or excluding the variant when it is absent. o Carrier screening – testing performed to determine an individual’s risk of passing a genetic mutation to their child. The purpose of carrier testing is to identify family members who are themselves unaffected but are at risk for producing affected children. o Clinical Utility – how the test results will alter patient management and ultimately lead to clinically important improvements in patient health outcomes. o Clinical Validity – the sensitivity, specificity, and positive and negative predictive values of the test. o Genetics – the branch of biology concerned with the study of genes, genetic variation, and heredity in living organisms. o Genetic testing – examination of the genetic information contained within cells performed on tissues or fluids, such as blood, skin, saliva, etc. The tests help a physician determine if a
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person
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• Genetic Testing for Non-Cancerous Disease o has a genetic disorder, is a carrier of a genetic disease, or has a predisposition to develop a genetic disorder. o Genomics – the branch of molecular biology concerned with the structure, function, evolution, and mapping of genomes. o Genotype – the genetic constitution of a cell, and therefore an organism or individual, which determines a specific characteristic (phenotype) of that cell/organism/individual. o Germline Mutation – the presence of an altered gene within the egg or sperm (germ cell) that can be inherited by subsequent generations. o Proteomics – the large-scale study of proteins produced by an organism or individual.
Procedure 3.1 Genetic testing is covered for a diagnosis of a heritable disease when the following criteria are met: a. The patient either displays clinical features (symptomatic), or is at direct risk of inheriting the mutation in question (pre‐symptomatic); and b. The result of the test will directly impact the treatment; and c. There is evidence that a better outcome will result for the patient when treatment changes are based on the results of the genetic test, and d. After history, physical examination, pedigree analysis, genetic counseling, and completion of conventional diagnostic studies, a definitive diagnosis remains uncertain; Or: e. Testing or screening is mandated by applicable law (e.g. newborn screening).
3.2 Genetic counseling may be performed by the following genetic specialists: a. Board‐certified/Board‐eligible medical geneticist (MD) b. Licensed advanced practice registered nurse in genetics (APRN) c. Under the signature of an MD or APRN:
- Master of Science degree in genetic counseling (MS)
Board‐certified/Board‐eligible genetic counselor (CGC)
3.3 Laboratories that perform genetic testing must be CLIA (Clinical Laboratory Improvement Amendments) certified.
3.4 In the case where AlohaCare lacks a specific medical policy addressing the requested genetic test, prior authorization is required. The information that must be provided with the prior authorization request must be sufficient to determine: a. The condition the patient has (or is at risk of inheriting); and b. The way in which treatment will be guided by the result of the genetic test; and c. The history, physical examination, pedigree analysis, genetic counseling, and conventional diagnostic study results that suggest the presence of a genetic condition, and have failed to determine the diagnosis; and d. For newer and emerging genetic tests, any peer-reviewed publications that support the analytic validity, clinical validity, and clinical utility of the genetic test requested.
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3.5 The following testing is covered without prior authorization:
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Genetic Testing for Non-Cancerous Disease a. Fragile X testing when:
- The result of the test will change clinical management; and
- One of the following: o Patient’s mother is a known carrier; or o Patient has intellectual disability, developmental delay, or autism spectrum disorder without an identified cause, or o Patient has a family history of fragile X syndrome and neurologic symptoms consistent with fragile X-associated tremor/ataxia syndrome (e.g. 50 years or older and develops progressive intention tremor, ataxia, memory loss, cognitive decline, and personality changes); or o Woman with primary ovarian failure under the age of 40 in whom fragile X- associated ovarian failure is suspected. b. Cystic Fibrosis (CF) screening when:
- A woman is pregnant, or considering becoming pregnant, and has not previously been screened, once in a lifetime screening for CF mutation carrier is covered; or
The reproductive partner of a woman who is a known CF carrier (see 1 above), once in a lifetime screening for CF is covered.
Limitations 4.1 Genetic testing for a specific inherited disease will be covered once per lifetime.
4.2 For a known deleterious mutation, AlohaCare covers a targeted single site analysis genetic test and not a full analysis (i.e., testing for the mutation that has been identified in the family).
4.3 Genetic testing is not covered if the results of genetic testing are for the medical management of family members who are not covered by AlohaCare.
4.4 For a gene panel test to be considered, each gene in the panel must have clinical utility for the patient tested.
4.5 The following genetic tests are not covered because they have not been shown to improve long-term health outcomes: a. Genetic testing to determine preterm labor; b. Genetic testing to determine warfarin sensitivity; c. Genetic testing for the diagnosis or risk assessment of Alzheimer's disease including but not limited to testing for, apolipoprotein E epsilon 4 allele, presenilin genes or amyloid precursor gene; d. Genetic testing for helicobacter pylori treatment; e. MTHFR polymorphism testing; f. Cystic fibrosis:
- Repeat carrier screening (more than once in a lifetime). Screening results should be documented and the test should not be repeated.
Complete analysis of the CFTR gene by DNA sequencing for routine carrier screening
4.6 The following expanded prenatal panel tests are not covered because the clinical utility has not
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been established (This is not an all-inclusive list): a. Myriad Foresight b. Invitae Broad Carrier Screen c. Invitae Comprehensive Carrier Screen d. Inherigen e. Inheritest f. Natera One Disease Panel g. Progenity Preparent or Resura
4.7 Home genetic testing, or direct-to-consumer genetic testing is not a covered benefit.
- Coding Information The following medical codes are relevant codes for diagnosis and procedures for genetic testing for non- cancerous disease and for informational purposes only. All the medical codes listed in this policy do not constitute or imply benefit coverage or provider reimbursement. Codes that do not require prior authorization: CPT Description 81220 CFTR (cystic fibrosis transmembrane conductance regulator) (e.g. cystic fibrosis) gene analysis; common variants 81243 FMR1 (fragile X mental retardation 1) (e.g. fragile X mental retardation) gene analysis; evaluation to detect abnormal alleles Codes that require prior authorization: CPT Description 81105 Human Platelet Antigen 1 genotyping (HPA-1), ITGB3 (integrin, beta 3 [platelet glycoprotein IIIa], antigen CD61 [GPIIIa]) (eg, neonatal alloimmune thrombocytopenia [NAIT], post-transfusion purpura), gene analysis, common variant, HPA-1a/b (L33P) 81106 Human Platelet Antigen 2 genotyping (HPA-2), GP1BA (glycoprotein Ib [platelet], alpha polypeptide [GPIba]) (eg, neonatal alloimmune thrombocytopenia [NAIT], post-transfusion purpura), gene analysis, common variant, HPA-2a/b (T145M) 81107 Human Platelet Antigen 3 genotyping (HPA-3), ITGA2B (integrin, alpha 2b [platelet glycoprotein IIb of IIb/IIIa complex], antigen CD41 [GPIIb]) (eg, neonatal alloimmune thrombocytopenia [NAIT], post-transfusion purpura), gene analysis, common variant, HPA-3a/b (I843S) 81108 Human Platelet Antigen 4 genotyping (HPA-4), ITGB3 (integrin, beta 3 [platelet glycoprotein IIIa], antigen CD61 [GPIIIa]) (eg, neonatal alloimmune thrombocytopenia [NAIT], post-transfusion purpura), gene analysis, common variant, HPA-4a/b (R143Q) 81109 Human Platelet Antigen 5 genotyping (HPA-5), ITGA2 (integrin, alpha 2 [CD49B, alpha 2 subunit of VLA-2 receptor] [GPIa]) (eg, neonatal alloimmune thrombocytopenia [NAIT], post-transfusion purpura), gene analysis, common variant (eg, HPA-5a/b (K505E)) 81110 Human Platelet Antigen 6 genotyping (HPA-6w), ITGB3 (integrin, beta 3 [platelet glycoprotein IIIa, antigen CD61] [GPIIIa]) (eg, neonatal alloimmune thrombocytopenia [NAIT], post-transfusion purpura), gene analysis, common variant, HPA-6a/b (R489Q)
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81111 Human Platelet Antigen 9 genotyping (HPA-9w), ITGA2B (integrin, alpha 2b [platelet glycoprotein IIb of IIb/IIIa complex, antigen CD41] [GPIIb]) (eg, neonatal alloimmune thrombocytopenia [NAIT], post-transfusion purpura), gene analysis, common variant, HPA-9a/b (V837M) 81112 Human Platelet Antigen 15 genotyping (HPA-15), CD109 (CD109 molecule) (eg, neonatal alloimmune thrombocytopenia [NAIT], post-transfusion purpura), gene analysis, common variant, HPA-15a/b (S682Y) 81161 DMD (dystrophin) (eg, Duchenne/Becker muscular dystrophy) deletion analysis, and duplication analysis, if performed 81171 AFF2 (AF4/FMR2 family, member 2 [FMR2]) (eg, fragile X mental retardation 2 [FRAXE]) gene analysis; evaluation to detect abnormal (eg, expanded) alleles 81172 AFF2 (AF4/FMR2 family, member 2 [FMR2]) (eg, fragile X mental retardation 2 [FRAXE]) gene analysis; characterization of alleles (eg, expanded size and methylation status) 81173 AR (androgen receptor) (eg, spinal and bulbar muscular atrophy, Kennedy disease, X chromosome inactivation) gene analysis; full gene sequence 81174 AR (androgen receptor) (eg, spinal and bulbar muscular atrophy, Kennedy disease, X chromosome inactivation) gene analysis; known familial variant 81177 ATN1 (atrophin 1) (eg, dentatorubral-pallidoluysian atrophy) gene analysis, evaluation to detect abnormal (eg, expanded) alleles 81178 ATXN1 (ataxin 1) (eg, spinocerebellar ataxia) gene analysis, evaluation to detect abnormal (eg, expanded) alleles 81179 ATXN2 (ataxin 2) (eg, spinocerebellar ataxia) gene analysis, evaluation to detect abnormal (eg, expanded) alleles 81180 ATXN3 (ataxin 3) (eg, spinocerebellar ataxia, Machado-Joseph disease) gene analysis, evaluation to detect abnormal (eg, expanded) alleles 81181 ATXN7 (ataxin 7) (eg, spinocerebellar ataxia) gene analysis, evaluation to detect abnormal (eg, expanded) alleles 81182 ATXN8OS (ATXN8 opposite strand [non-protein coding]) (eg, spinocerebellar ataxia) gene analysis, evaluation to detect abnormal (eg, expanded) alleles 81183 ATXN10 (ataxin 10) (eg, spinocerebellar ataxia) gene analysis, evaluation to detect abnormal (eg, expanded) alleles 81184 CACNA1A (calcium voltage-gated channel subunit alpha1 A) (eg, spinocerebellar ataxia) gene analysis; evaluation to detect abnormal (eg, expanded) alleles 81185 CACNA1A (calcium voltage-gated channel subunit alpha1 A) (eg, spinocerebellar ataxia) gene analysis; full gene sequence 81186 CACNA1A (calcium voltage-gated channel subunit alpha1 A) (eg, spinocerebellar ataxia) gene analysis; known familial variant 81187 CNBP (CCHC-type zinc finger nucleic acid binding protein) (eg, myotonic dystrophy type 2) gene analysis, evaluation to detect abnormal (eg, expanded) alleles 81188 CSTB (cystatin B) (eg, Unverricht-Lundborg disease) gene analysis; evaluation to detect abnormal (eg, expanded) alleles
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81189 CSTB (cystatin B) (eg, Unverricht-Lundborg disease) gene analysis; full gene sequence 81190 CSTB (cystatin B) (eg, Unverricht-Lundborg disease) gene analysis; known familial variant(s) 81200 ASPA (aspartoacylase) (eg, Canavan disease) gene analysis, common variants (eg, E285A, Y231X) 81204 AR (androgen receptor) (eg, spinal and bulbar muscular atrophy, Kennedy disease, X chromosome inactivation) gene analysis; characterization of alleles (eg, expanded size or methylation status) 81205 BCKDHB (branched-chain keto acid dehydrogenase E1, beta polypeptide) (eg, maple syrup urine disease) gene analysis, common variants (eg, R183P, G278S, E422X) 81209 BLM (Bloom syndrome, RecQ helicase-like) (eg, Bloom syndrome) gene analysis, 2281del6ins7 variant 81221 CFTR (cystic fibrosis transmembrane conductance regulator) (eg, cystic fibrosis) gene analysis; known familial variants 81222 CFTR (cystic fibrosis transmembrane conductance regulator) (eg, cystic fibrosis) gene analysis; duplication/deletion variants 81223 CFTR (cystic fibrosis transmembrane conductance regulator) (eg, cystic fibrosis) gene analysis; full gene sequence 81224 CFTR (cystic fibrosis transmembrane conductance regulator) (eg, cystic fibrosis) gene analysis; intron 8 poly-T analysis (eg, male infertility) 81225 CYP2C19 (cytochrome P450, family 2, subfamily C, polypeptide 19) (eg, drug metabolism), gene analysis, common variants (eg, 2, 3, 4, 8, 17) 81226 CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) (eg, drug metabolism), gene analysis, common variants (eg, 2, 3, 4, 5, 6, 9, 10, 17, 19, 29, 35, 41, 1XN, 2XN, 4XN) 81227 CYP2C9 (cytochrome P450, family 2, subfamily C, polypeptide 9) (eg, drug metabolism), gene analysis, common variants (eg, 2, 3, 5, 6) 81228 Cytogenomic constitutional (genome-wide) microarray analysis; interrogation of genomic regions for copy number variants (eg, bacterial artificial chromosome [BAC] or oligo-based comparative genomic hybridization [CGH] microarray analysis) 81229 Cytogenomic constitutional (genome-wide) microarray analysis; interrogation of genomic regions for copy number and single nucleotide polymorphism (SNP) variants for chromosomal abnormalities 81230 CYP3A4 (cytochrome P450 family 3 subfamily A member 4) (eg, drug metabolism), gene analysis, common variant(s) (eg, 2, 22) 81231 CYP3A5 (cytochrome P450 family 3 subfamily A member 5) (eg, drug metabolism), gene analysis, common variants (eg, 2, 3, 4, 5, 6, 7) 81232 DPYD (dihydropyrimidine dehydrogenase) (eg, 5-fluorouracil/5-FU and capecitabine drug metabolism), gene analysis, common variant(s) (eg, 2A, 4, 5, 6) 81234 DMPK (DM1 protein kinase) (eg, myotonic dystrophy type 1) gene analysis; evaluation to detect abnormal (expanded) alleles 81238 F9 (coagulation factor IX) (eg, hemophilia B), full gene sequence 81239 DMPK (DM1 protein kinase) (eg, myotonic dystrophy type 1) gene analysis; characterization of alleles (eg, expanded size)
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81240 F2 (prothrombin, coagulation factor II) (eg, hereditary hypercoagulability) gene analysis, 20210G>A variant 81241 F5 (coagulation factor V) (eg, hereditary hypercoagulability) gene analysis, Leiden variant 81242 FANCC (Fanconi anemia, complementation group C) (eg, Fanconi anemia, type C) gene analysis, common variant (eg, IVS4+4A>T) 81244 FMR1 (fragile X mental retardation 1) (eg, fragile X mental retardation) gene analysis; characterization of alleles (eg, expanded size and promoter methylation status) 81247 G6PD (glucose-6-phosphate dehydrogenase) (eg, hemolytic anemia, jaundice), gene analysis; common variant(s) (eg, A, A-) 81248 G6PD (glucose-6-phosphate dehydrogenase) (eg, hemolytic anemia, jaundice), gene analysis; known familial variant(s) 81249 G6PD (glucose-6-phosphate dehydrogenase) (eg, hemolytic anemia, jaundice), gene analysis; full gene sequence 81250 G6PC (glucose-6-phosphatase, catalytic subunit) (eg, Glycogen storage disease, type 1a, von Gierke disease) gene analysis, common variants (eg, R83C, Q347X) 81251 GBA (glucosidase, beta, acid) (eg, Gaucher disease) gene analysis, common variants (eg, N370S, 84GG, L444P, IVS2+1G>A) 81252 GJB2 (gap junction protein, beta 2, 26kDa, connexin 26) (eg, nonsyndromic hearing loss) gene analysis; full gene sequence 81253 GJB2 (gap junction protein, beta 2, 26kDa, connexin 26) (eg, nonsyndromic hearing loss) gene analysis; known familial variants 81254 GJB6 (gap junction protein, beta 6, 30kDa, connexin 30) (eg, nonsyndromic hearing loss) gene analysis, common variants (eg, 309kb [del(GJB6-D13S1830)] and 232kb [del(GJB6-D13S1854)]) 81255 HEXA (hexosaminidase A [alpha polypeptide]) (eg, Tay-Sachs disease) gene analysis, common variants (eg, 1278insTATC, 1421+1G>C, G269S) 81256 HFE (hemochromatosis) (eg, hereditary hemochromatosis) gene analysis, common variants (eg, C282Y, H63D) 81257 HBA1/HBA2 (alpha globin 1 and alpha globin 2) (eg, alpha thalassemia, Hb Bart hydrops fetalis syndrome, HbH disease), gene analysis; common deletions or variant (eg, Southeast Asian, Thai, Filipino, Mediterranean, alpha3.7, alpha4.2, alpha20.5, Constant Spring) 81258 HBA1/HBA2 (alpha globin 1 and alpha globin 2) (eg, alpha thalassemia, Hb Bart hydrops fetalis syndrome, HbH disease), gene analysis; known familial variant 81259 HBA1/HBA2 (alpha globin 1 and alpha globin 2) (eg, alpha thalassemia, Hb Bart hydrops fetalis syndrome, HbH disease), gene analysis; full gene sequence 81260 IKBKAP (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase complex-associated protein) (eg, familial dysautonomia) gene analysis, common variants (eg, 2507+6T>C, R696P) 81261 IGH@ (Immunoglobulin heavy chain locus) (eg, leukemias and lymphomas, B-cell), gene rearrangement analysis to detect abnormal clonal population(s); amplified methodology (eg, polymerase chain reaction) 81265 Comparative analysis using Short Tandem Repeat (STR) markers; patient and comparative specimen
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(eg, pre-transplant recipient and donor germline testing, post-transplant non-hematopoietic recipient germline [eg, buccal swab or other germline tissue sample] and donor testing, twin zygosity testing, or maternal cell contamination of fetal cells) 81266 Comparative analysis using Short Tandem Repeat (STR) markers; each additional specimen (eg, additional cord blood donor, additional fetal samples from different cultures, or additional zygosity in multiple birth pregnancies) (List separately in addition to code for primary procedure) 81267 Chimerism (engraftment) analysis, post transplantation specimen (eg, hematopoietic stem cell), includes comparison to previously performed baseline analyses; without cell selection 81268 Chimerism (engraftment) analysis, post transplantation specimen (eg, hematopoietic stem cell), includes comparison to previously performed baseline analyses; with cell selection (eg, CD3, CD33), each cell type 81269 HBA1/HBA2 (alpha globin 1 and alpha globin 2) (eg, alpha thalassemia, Hb Bart hydrops fetalis syndrome, HbH disease), gene analysis; duplication/deletion variants 81271 HTT (huntingtin) (eg, Huntington disease) gene analysis; evaluation to detect abnormal (eg, expanded) alleles 81274 HTT (huntingtin) (eg, Huntington disease) gene analysis; characterization of alleles (eg, expanded size) 81283 IFNL3 (interferon, lambda 3) (eg, drug response), gene analysis, rs12979860 variant 81284 FXN (frataxin) (eg, Friedreich ataxia) gene analysis; evaluation to detect abnormal (expanded) alleles 81285 FXN (frataxin) (eg, Friedreich ataxia) gene analysis; characterization of alleles (eg, expanded size) 81286 FXN (frataxin) (eg, Friedreich ataxia) gene analysis; full gene sequence 81289 FXN (frataxin) (eg, Friedreich ataxia) gene analysis; known familial variant(s) 81290 MCOLN1 (mucolipin 1) (eg, Mucolipidosis, type IV) gene analysis, common variants (eg, IVS3- 2A>G, del6.4kb) 81302 MECP2 (methyl CpG binding protein 2) (eg, Rett syndrome) gene analysis; full sequence analysis 81303 MECP2 (methyl CpG binding protein 2) (eg, Rett syndrome) gene analysis; known familial variant 81304 MECP2 (methyl CpG binding protein 2) (eg, Rett syndrome) gene analysis; duplication/deletion variants 81306 NUDT15 (nudix hydrolase 15) (eg, drug metabolism) gene analysis, common variant(s) (eg, 2, 3, 4, 5, *6) 81312 PABPN1 (poly[A] binding protein nuclear 1) (eg, oculopharyngeal muscular dystrophy) gene analysis, evaluation to detect abnormal (eg, expanded) alleles 81321 PTEN (phosphatase and tensin homolog) (eg, Cowden syndrome, PTEN hamartoma tumor syndrome) gene analysis; full sequence analysis 81322 PTEN (phosphatase and tensin homolog) (eg, Cowden syndrome, PTEN hamartoma tumor syndrome) gene analysis; known familial variant 81323 PTEN (phosphatase and tensin homolog) (eg, Cowden syndrome, PTEN hamartoma tumor syndrome) gene analysis; duplication/deletion variant 81324 PMP22 (peripheral myelin protein 22) (eg, Charcot-Marie-Tooth, hereditary neuropathy with liability to pressure palsies) gene analysis; duplication/deletion analysis
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81325 PMP22 (peripheral myelin protein 22) (eg, Charcot-Marie-Tooth, hereditary neuropathy with liability to pressure palsies) gene analysis; full sequence analysis 81326 PMP22 (peripheral myelin protein 22) (eg, Charcot-Marie-Tooth, hereditary neuropathy with liability to pressure palsies) gene analysis; known familial variant 81328 SLCO1B1 (solute carrier organic anion transporter family, member 1B1) (eg, adverse drug reaction), gene analysis, common variant(s) (eg, 5) 81329 SMN1 (survival of motor neuron 1, telomeric) (eg, spinal muscular atrophy) gene analysis; dosage/deletion analysis (eg, carrier testing), includes SMN2 (survival of motor neuron 2, centromeric) analysis, if performed 81330 SMPD1(sphingomyelin phosphodiesterase 1, acid lysosomal) (eg, Niemann-Pick disease, Type A) gene analysis, common variants (eg, R496L, L302P, fsP330) 81331 SNRPN/UBE3A (small nuclear ribonucleoprotein polypeptide N and ubiquitin protein ligase E3A) (eg, Prader-Willi syndrome and/or Angelman syndrome), methylation analysis 81332 SERPINA1 (serpin peptidase inhibitor, clade A, alpha-1 antiproteinase, antitrypsin, member 1) (eg, alpha-1-antitrypsin deficiency), gene analysis, common variants (eg, S and Z) 81333 TGFBI (transforming growth factor beta-induced) (eg, corneal dystrophy) gene analysis, common variants (eg, R124H, R124C, R124L, R555W, R555Q) 81335 TPMT (thiopurine S-methyltransferase) (eg, drug metabolism), gene analysis, common variants (eg, 2, 3) 81336 SMN1 (survival of motor neuron 1, telomeric) (eg, spinal muscular atrophy) gene analysis; full gene sequence 81337 SMN1 (survival of motor neuron 1, telomeric) (eg, spinal muscular atrophy) gene analysis; known familial sequence variant(s) 81343 PPP2R2B (protein phosphatase 2 regulatory subunit Bbeta) (eg, spinocerebellar ataxia) gene analysis, evaluation to detect abnormal (eg, expanded) alleles 81344 TBP (TATA box binding protein) (eg, spinocerebellar ataxia) gene analysis, evaluation to detect abnormal (eg, expanded) alleles 81346 TYMS (thymidylate synthetase) (eg, 5-fluorouracil/5-FU drug metabolism), gene analysis, common variant(s) (eg, tandem repeat variant) 81350 UGT1A1 (UDP glucuronosyltransferase 1 family, polypeptide A1) (eg, irinotecan metabolism), gene analysis, common variants (eg, 28, 36, 37) 81355 VKORC1 (vitamin K epoxide reductase complex, subunit 1) (eg, warfarin metabolism), gene analysis, common variant(s) (eg, -1639G>A, c.173+1000C>T) 81361 HBB (hemoglobin, subunit beta) (eg, sickle cell anemia, beta thalassemia, hemoglobinopathy); common variant(s) (eg, HbS, HbC, HbE) 81362 HBB (hemoglobin, subunit beta) (eg, sickle cell anemia, beta thalassemia, hemoglobinopathy); known familial variant(s) 81363 HBB (hemoglobin, subunit beta) (eg, sickle cell anemia, beta thalassemia, hemoglobinopathy); duplication/deletion variant(s) 81364 HBB (hemoglobin, subunit beta) (eg, sickle cell anemia, beta thalassemia, hemoglobinopathy); full
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gene sequence 81400 MOLECULAR PATHOLOGY PROCEDURE LEVEL 1 81401 MOLECULAR PATHOLOGY PROCEDURE LEVEL 2 81402 MOLECULAR PATHOLOGY PROCEDURE LEVEL 3 81403 MOLECULAR PATHOLOGY PROCEDURE LEVEL 4 81404 MOLECULAR PATHOLOGY PROCEDURE LEVEL 5 81405 MOLECULAR PATHOLOGY PROCEDURE LEVEL 6 81406 MOLECULAR PATHOLOGY PROCEDURE LEVEL 7 81407 Molecular pathology procedure, Level 8 (eg, analysis of 26-50 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of >50 exons, sequence analysis of multiple genes on one platform) 81408 MOLECULAR PATHOLOGY PROCEDURE LEVEL 9 81410 Aortic dysfunction or dilation (eg, Marfan syndrome, Loeys Dietz syndrome, Ehler Danlos syndrome type IV, arterial tortuosity syndrome); genomic sequence analysis panel, must include sequencing of at least 9 genes, including FBN1, TGFBR1, TGFBR2, COL3A1, MYH11, ACTA2, SLC2A10, SMAD3, and MYLK 81411 Aortic dysfunction or dilation (eg, Marfan syndrome, Loeys Dietz syndrome, Ehler Danlos syndrome type IV, arterial tortuosity syndrome); duplication/deletion analysis panel, must include analyses for TGFBR1, TGFBR2, MYH11, and COL3A1 81412 Ashkenazi Jewish associated disorders (eg, Bloom syndrome, Canavan disease, cystic fibrosis, familial dysautonomia, Fanconi anemia group C, Gaucher disease, Tay-Sachs disease), genomic sequence analysis panel, must include sequencing of at least 9 genes, including ASPA, BLM, CFTR, FANCC, GBA, HEXA, IKBKAP, MCOLN1, and SMPD1 81413 Cardiac ion channelopathies (eg, Brugada syndrome, long QT syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia); genomic sequence analysis panel, must include sequencing of at least 10 genes, including ANK2, CASQ2, CAV3, KCNE1, KCNE2, KCNH2, KCNJ2, KCNQ1, RYR2, and SCN5A 81414 Cardiac ion channelopathies (eg, Brugada syndrome, long QT syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia); duplication/deletion gene analysis panel, must include analysis of at least 2 genes, including KCNH2 and KCNQ1 81415 Exome (eg, unexplained constitutional or heritable disorder or syndrome); sequence analysis 81416 Exome (eg, unexplained constitutional or heritable disorder or syndrome); sequence analysis, each comparator exome (eg, parents, siblings) (List separately in addition to code for primary procedure) 81417 Exome (eg, unexplained constitutional or heritable disorder or syndrome); re-evaluation of previously obtained exome sequence (eg, updated knowledge or unrelated condition/syndrome) 81422 Fetal chromosomal microdeletion(s) genomic sequence analysis (eg, DiGeorge syndrome, Cri-du-chat syndrome), circulating cell-free fetal DNA in maternal blood 81425 Genome (eg, unexplained constitutional or heritable disorder or syndrome); sequence analysis 81426 Genome (eg, unexplained constitutional or heritable disorder or syndrome); sequence analysis, each comparator genome (eg, parents, siblings) (List separately in addition to code for primary procedure)
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81427 Genome (eg, unexplained constitutional or heritable disorder or syndrome); re-evaluation of previously obtained genome sequence (eg, updated knowledge or unrelated condition/syndrome) 81430 Hearing loss (eg, nonsyndromic hearing loss, Usher syndrome, Pendred syndrome); genomic sequence analysis panel, must include sequencing of at least 60 genes, including CDH23, CLRN1, GJB2, GPR98, MTRNR1, MYO7A, MYO15A, PCDH15, OTOF, SLC26A4, TMC1, TMPRSS3, USH1C, USH1G, USH2A, and WFS1 81431 Hearing loss (eg, nonsyndromic hearing loss, Usher syndrome, Pendred syndrome); duplication/deletion analysis panel, must include copy number analyses for STRC and DFNB1 deletions in GJB2 and GJB6 genes 81432 Hereditary breast cancer-related disorders (eg, hereditary breast cancer, hereditary ovarian cancer, hereditary endometrial cancer); genomic sequence analysis panel, must include sequencing of at least 10 genes, always including BRCA1, BRCA2, CDH1, MLH1, MSH2, MSH6, PALB2, PTEN, STK11, and TP53 81433 Hereditary breast cancer-related disorders (eg, hereditary breast cancer, hereditary ovarian cancer, hereditary endometrial cancer); duplication/deletion analysis panel, must include analyses for BRCA1, BRCA2, MLH1, MSH2, and STK11 81434 Hereditary retinal disorders (eg, retinitis pigmentosa, Leber congenital amaurosis, cone-rod dystrophy), genomic sequence analysis panel, must include sequencing of at least 15 genes, including ABCA4, CNGA1, CRB1, EYS, PDE6A, PDE6B, PRPF31, PRPH2, RDH12, RHO, RP1, RP2, RPE65, RPGR, and USH2A 81437 Hereditary neuroendocrine tumor disorders (eg, medullary thyroid carcinoma, parathyroid carcinoma, malignant pheochromocytoma or paraganglioma); genomic sequence analysis panel, must include sequencing of at least 6 genes, including MAX, SDHB, SDHC, SDHD, TMEM127, and VHL 81438 Hereditary neuroendocrine tumor disorders (eg, medullary thyroid carcinoma, parathyroid carcinoma, malignant pheochromocytoma or paraganglioma); duplication/deletion analysis panel, must include analyses for SDHB, SDHC, SDHD, and VHL 81439 Hereditary cardiomyopathy (eg, hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy), genomic sequence analysis panel, must include sequencing of at least 5 cardiomyopathy-related genes (eg, DSG2, MYBPC3, MYH7, PKP2, TTN) 81440 Nuclear encoded mitochondrial genes (eg, neurologic or myopathic phenotypes), genomic sequence panel, must include analysis of at least 100 genes, including BCS1L, C10orf2, COQ2, COX10, DGUOK, MPV17, OPA1, PDSS2, POLG, POLG2, RRM2B, SCO1, SCO2, SLC25A4, SUCLA2, SUCLG1, TAZ, TK2, and TYMP 81442 Noonan spectrum disorders (eg, Noonan syndrome, cardio-facio-cutaneous syndrome, Costello syndrome, LEOPARD syndrome, Noonan-like syndrome), genomic sequence analysis panel, must include sequencing of at least 12 genes, including BRAF, CBL, HRAS, KRAS, MAP2K1, MAP2K2, NRAS, PTPN11, RAF1, RIT1, SHOC2, and SOS1 81443 Genetic testing for severe inherited conditions (eg, cystic fibrosis, Ashkenazi Jewish-associated disorders [eg, Bloom syndrome, Canavan disease, Fanconi anemia type C, mucolipidosis type VI, Gaucher disease, Tay-Sachs disease], beta hemoglobinopathies, phenylketonuria, galactosemia), genomic sequence analysis panel, must include sequencing of at least 15 genes (eg, ACADM, ARSA,
Medical Policy Genetic Testing for Non-Cancerous Disease Genetic Testing for Non-Cancerous Disease
Review/Revision Date: 04/26/2022Page 12 of 15
ASPA, ATP7B, BCKDHA, BCKDHB, BLM, CFTR, DHCR7, FANCC, G6PC, GAA, GALT, GBA, GBE1, HBB, HEXA, IKBKAP, MCOLN1, PAH) 81448 Hereditary peripheral neuropathies (eg, Charcot-Marie-Tooth, spastic paraplegia), genomic sequence analysis panel, must include sequencing of at least 5 peripheral neuropathy-related genes (eg, BSCL2, GJB1, MFN2, MPZ, REEP1, SPAST, SPG11, SPTLC1) 81460 Whole mitochondrial genome (eg, Leigh syndrome, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes [MELAS], myoclonic epilepsy with ragged-red fibers [MERFF], neuropathy, ataxia, and retinitis pigmentosa [NARP], Leber hereditary optic neuropathy [LHON]), genomic sequence, must include sequence analysis of entire mitochondrial genome with heteroplasmy detection 81465 Whole mitochondrial genome large deletion analysis panel (eg, Kearns-Sayre syndrome, chronic progressive external ophthalmoplegia), including heteroplasmy detection, if performed 81470 X-linked intellectual disability (XLID) (eg, syndromic and non-syndromic XLID); genomic sequence analysis panel, must include sequencing of at least 60 genes, including ARX, ATRX, CDKL5, FGD1, FMR1, HUWE1, IL1RAPL, KDM5C, L1CAM, MECP2, MED12, MID1, OCRL, RPS6KA3, and SLC16A2 81471 X-linked intellectual disability (XLID) (eg, syndromic and non-syndromic XLID); duplication/deletion gene analysis, must include analysis of at least 60 genes, including ARX, ATRX, CDKL5, FGD1, FMR1, HUWE1, IL1RAPL, KDM5C, L1CAM, MECP2, MED12, MID1, OCRL, RPS6KA3, and SLC16A2 81479 Unlisted molecular pathology procedure 81493 Coronary artery disease, mRNA, gene expression profiling by real-time RT-PCR of 23 genes, utilizing whole peripheral blood, algorithm reported as a risk score 81595 Cardiology (heart transplant), mRNA, gene expression profiling by real-time quantitative PCR of 20 genes (11 content and 9 housekeeping), utilizing subfraction of peripheral blood, algorithm reported as a rejection risk score 81599 Unlisted multianalyte assay with algorithmic analysis 0001U Red blood cell antigen typing, DNA, human erythrocyte antigen gene analysis of 35 antigens from 11 blood groups, utilizing whole blood, common RBC alleles reported 0012U Germline disorders, gene rearrangement detection by whole genome next-generation sequencing, DNA, whole blood, report of specific gene rearrangement(s) 0029U Drug metabolism (adverse drug reactions and drug response), targeted sequence analysis (ie, CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4, CYP3A5, CYP4F2, SLCO1B1, VKORC1 and rs12777823) 0031U CYP1A2 (cytochrome P450 family 1, subfamily A, member 2) (eg, drug metabolism) gene analysis, common variants (ie, 1F, 1K, 6, 7) 0032U COMT (catechol-O-methyltransferase) (eg, drug metabolism) gene analysis ,c.472G>A (rs4680) variant 0033U HTR2A (5-hydroxytryptamine receptor 2A), HTR2C (5-hydroxytryptamine receptor 2C) (eg, citalopram metabolism) gene analysis, common variants (i.e., HTR2A rs7997012 [c.614-2211T>C], HTR2C rs3813929 [c.- 759C>T] and rs1414334 [c.551-3008C>G])
Medical Policy Genetic Testing for Non-Cancerous Disease Genetic Testing for Non-Cancerous Disease
Review/Revision Date: 04/26/2022Page 13 of 15
0034U TPMT (thiopurine S-methyltransferase), NUDT15 (nudix hydroxylase 15) (eg, thiopurine metabolism) gene analysis, common variants (i.e., TPMT 2, 3A, 3B, 3C, 4, 5, 6, 8, 12; NUDT15 3, 4, 5) 0036U Exome (ie, somatic mutations), paired formalin-fixed paraffin-embedded tumor tissue and normal specimen, sequence analyses 0039U Deoxyribonucleic acid (DNA) antibody, double stranded, high avidity 0055U Cardiology (heart transplant), cell-free DNA, PCR assay of 96 DNA target sequences (94 single nucleotide polymorphism targets and two control targets), plasma 0070U CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) (eg, drug metabolism) gene analysis, common and select rare variants (ie, 2, 3, 4, 4N, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14A, 14B, 15, 17, 29, 35, 36, 41, 57, 61, 63, 68, 83, *xN) 0071U CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) (eg, drug metabolism) gene analysis, full gene sequence (List separately in addition to code for primary procedure) 0072U CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) (eg, drug metabolism) gene analysis, targeted sequence analysis (ie, CYP2D6-2D7 hybrid gene) (List separately in addition to code for primary procedure) 0073U CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) (eg, drug metabolism) gene analysis, targeted sequence analysis (ie, CYP2D7-2D6 hybrid gene) (List separately in addition to code for primary procedure) 0074U CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) (eg, drug metabolism) gene analysis, targeted sequence analysis (ie, non-duplicated gene when duplication/multiplication is trans) (List separately in addition to code for primary procedure) 0075U CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) (eg, drug metabolism) gene analysis, targeted sequence analysis (ie, 5’ gene duplication/multiplication) (List separately in addition to code for primary procedure) 0078U Pain management (opioid-use disorder) genotyping panel, 16 common variants (ie, ABCB1, COMT, DAT1, DBH, DOR, DRD1, DRD2, DRD4, GABA, GAL, HTR2A, HTTLPR, MTHFR, MUOR, OPRK1, OPRM1), buccal swab or other germline tissue sample, algorithm reported as positive or negative risk of opioid-use disorder
HCPCS Description S3842 Genetic testing for Von Hippel-Lindau disease S3845 Genetic testing for alpha-thalassemia S3846 Genetic testing for hemoglobin E beta-thalassemia S3849 Genetic testing for Niemann-Pick disease S3850 Genetic testing for sickle cell anemia S3853 Genetic testing for myotonic muscular dystrophy S3861 Genetic testing, sodium channel, voltage-gated, type v, alpha subunit (scn5a) and variants for suspected Brugada syndrome S3865 Comprehensive gene sequence analysis for hypertrophic cardiomyopathy S3866 Genetic analysis for a specific gene mutation for hypertrophic cardiomyopathy (HCM) in an
Medical Policy Genetic Testing for Non-Cancerous Disease Genetic Testing for Non-Cancerous Disease
Review/Revision Date: 04/26/2022Page 14 of 15
Not covered: Description 81227 CYP2C9 (cytochrome P450, family 2, subfamily C, polypeptide 9) (e.g., drug metabolism), gene analysis, common variants (e.g., 2, 3, 5, 6) used in warfarin testing 81291 MTHFR (5, 10-methylenetetrahydrofolate reductase) (e.g., hereditary hypercoagulability) gene analysis, common variants (e.g., 677T, 1298C) 81355 VKORC1 (vitamin K epoxide reductase complex, subunit 1) (e.g., warfarin metabolism), gene analysis, common variants (e.g., -1639/3673) S3852 DNA analysis for APOE epsilon 4 allele for susceptibility to Alzheimer's disease 0009M Fetal aneuploidy (trisomy 21, and 18) DNA sequence analysis of selected regions using maternal plasma, algorithm reported as a risk score for each trisomy 0030U Drug metabolism (warfarin drug response), targeted sequence analysis (i.e., CYP2C9, CYP4F2, VKORC1, rs12777823) 0060U Twin zygosity, genomic-targeted sequence analysis of chromosome 2, using circulating cell-free fetal DNA in maternal blood 0079U Comparative DNA analysis using multiple selected single-nucleotide polymorphisms (SNPs), urine and buccal DNA, for specimen identity verification
- References/Resources 6.1 National Human Genome Research Institute-National Institutes of Health. Coverage and Reimbursement of Genetic Tests. Last updated: August 15, 2019. http://www.genome.gov/19016729 6.2 Auffray C, Griffin JL, Khoury MJ, Lupski JR, Schwab M. Ten years of Genome Medicine. Genome Med. 2019;11(1):7. Published 2019 Feb 15. doi:10.1186/s13073-019-0618-x https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376775/ 6.3 National Human Genome Research Institute-National Institutes of Health. Regulation of Genetic Tests. Last updated: January 17, 2018. http://www.genome.gov/10002335 6.4 ACOG Committee on Genetics Opinion; Carrier screening for Genetic Conditions, March 2017 (Reaffirmed 2019) https://www.acog.org/-/media/Committee-Opinions/Committee-on- Genetics/co691.pdf?dmc=1&ts=20191003T0248298865 6.5 ACOG Committee o Genetics Opinion, Microarrays and Next-Generation Sequencing Technology: The Use of Advanced Genetic Diagnostic Tools in Obstetrics and Gynecology, December 2016 https://www.acog.org/Clinical-Guidance-and-Publications/Committee-Opinions/Committee-on- Genetics/Microarrays-and-Next-Generation-Sequencing-Technology 6.6 ACMG Practice Guideline: Lack of Evidence for MTHFR Polymorphism Testing. Genet Med 2013:15(2):153–156. https://www.nature.com/articles/gim2012165.pdf 6.7 Khoury MJ, Feero WG, Reyes M, et al. The genomic applications in practice and prevention individual with a known HCM mutation in the family
Medical Policy Genetic Testing for Non-Cancerous Disease
Review/Revision Date: 04/26/2022Page 15 of 15
Genetic Testing for Non-Cancerous Disease network. Genet Med. 2009 July; 11(7): 488-494. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743616/pdf/pmcce8.pdf 6.8 Sun F, Bruening W, Erinoff E, et al [ECRI Institute]. Addressing Challenges in Genetic Test Evaluation. Evaluation Frameworks and Assessment of Analytic Validity [Internet]. U.S. Department of Health and Human Services-Agency for Healthcare Research and Quality (AHRQ). AHRQ Publication No. 11-EHC048-EF June 2011. Published 06/16/2011. http://www.ncbi.nlm.nih.gov/books/NBK56750/pdf/Bookshelf_NBK56750.pdf 6.9 Sun F, Bruening W, Uhl S, et al. [ECRI Institute]. Quality, Regulation and Clinical Utility of Laboratory-developed Molecular Tests [Internet]. U.S. Department of Health and Human Services-Agency for Healthcare Research and Quality (AHRQ). Technology Assessment. 2010 May 19 http://www.cms.gov/Medicare/Coverage/DeterminationProcess/downloads/id72TA.pdf 6.10 American Geriatrics Society Ethics Committee. Genetic Testing for late-onset Alzheimer’s Disease. J Am Geriatrics Soc. 2001 Dec; 49(2):225-226. http://onlinelibrary.wiley.com/doi/10.1046/j.1532-5415.2001.49998.x/pdf,
- Review/Revision History Date of – New policy 1/1/2016 9/29/2019 – Added definitions, updated references, updated codes, new template, clarified information required for PA, made non-covered tests more specific, removed PA for CF carrier screening. 04/26/2024 - Retired
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