CAM 166

General Genetic Testing, Germline Disorders

Category:Laboratory   Last Reviewed:January 2020
Department(s):Medical Affairs   Next Review:April 2020
Original Date:April 2017    

Description 
Germline mutation is a gene change in a body's reproductive cell (egg or sperm) that becomes incorporated into the DNA of every cell in the body of the offspring. Germline mutations are passed on from parents to offspring. Also called hereditary mutation. (National Cancer Institute 2017)

Genetic testing is a type of diagnostic testing that identifies changes in chromosomes, or genes. Genetic testing is used to confirm or rule out a suspected genetic condition or to help determine likelihood of developing or passing on a genetic disorder (National Institute of Health, 2017). 

Several methods can be used for genetic testing: 

Molecular genetic tests (or gene tests) study single genes or short lengths of DNA to identify variations or mutations that lead to a genetic disorder. 

Chromosomal genetic tests analyze whole chromosomes or long lengths of DNA to see if there are large genetic changes, such as an extra copy of a chromosome, that cause a genetic condition. (National Institute of Health 2017)

Background
Individuals with a germline genetic mutation may have an increased risk of certain inherited disorders. Germline testing is performed to confirm or rule out a genetic mutation causing a disorder or help determine a person's chance of developing or passing on a genetic disorder. Germline testing also allows for the initiation of preventive measures to reduce the likelihood of developing of an inherited disorder, or limiting the severity of symptoms,. Germline mutation testing typically involves testing of a sample from blood, body fluids, or tissues.

Policy  
Note: This policy addresses the general use of germline genetic testing and applies to all tests for which a specific policy is not available.

  1. Genetic counseling is considered MEDICALLY NECESSARY AND IS REQUIRED (IF TESTING IS NOT BEING ORDERED BY A SPECIALIST IN THE DISEASE PROCESS IN QUESTION (e.g. endocrinologist and maturity onset diabetes of youth gene evaluation)) for individuals prior to and after undergoing genetic testing for diagnostic, carrier, and/or risk assessment purposes.
  2. Genetic testing of the individual's genome for inherited diseases is considered MEDICALLY NECESSARY, once per patient lifetime, when the following criteria are met:
    • The individual for whom the test is requested is either:
      • Is currently symptomatic with suspicion of a known genetic disease where knowledge of mutation will assist in diagnosis, treatment, or procreative management , OR
      • Is currently asymptomatic but is judged to be at significant risk for an inherited disorder or cancer risk factor based on family history and/or ethnicity, AND, if being tested for risk of an adult-onset condition is at or above the age of majority, (e.g., 18 years), unless there is documented evidence that early intervention during childhood may prevent disease severity or time of disease onset, OR
      • Is asymptomatic but judged to be at risk as a carrier of an inherited disorder or cancer risk factor based on family history and/or ethnicity AND would benefit from procreative management
    • Regarding the test being considered ALL of the following are MET:
      • Scientific literature shows association of specific a gene mutation (or mutations) is associated with the disease in question and is clinically actionable (there is clinical utility) with non-investigational treatment; AND   
      • Other testing for the disease is equivocal or does not exist and confirmation of gene mutation is standard of care for the disease state; AND
      • Disease in question is associated with significant morbidity and/or mortality; AND
      • Results of testing can impact clinical management via surveillance or treatment strategies and will guide decisions on healthcare management to mitigate symptoms or progression of the disorder.
    • Genetic testing of an individual’s genome for inherited diseases is considered INVESTIGATIONAL in the following situations:
      • For risk assessment of an individual’s genome when the criteria defined in the MNC criteria above are not met
      • For inherited disease diagnosis or carrier assessment using panels of genes that include genes outside of those specifically related to the disease being investigated
      • Repeat germline testing of a unique gene using the identical method of gene analysis
      • Testing as a screening tool in the general population
      • Direct-to-consumer genetic testing (e.g. mail order, online ordering, pharmacy, retail)
  3. Germline multi-gene panel testing (See Note 1), defined as multiple gene tests for a medical condition or symptoms/non-specific presentation run on one testing platform,is considered MEDICALLY NECESSARY according to the guidelines in the preceding coverage criteria and the reimbursement limitations (see section regarding Reimbursement below). 

Reimbursement  

  1. If a procedure code is available for the multi-gene panel test, then this code is to be utilized (i.e., 81442 Noonan spectrum disorders genomic sequence analysis panel).
  2. If there is not a specific next generation sequencing procedure code that represents the requested test, the procedure may be represented by a maximum of ONE unit of 81479 [unlisted molecular pathology procedure] (i.e., 81479 X 1 should account for all remaining gene testing) OR All genes tested on the panel must be represented by ALL appropriate Molecular Pathology Tier 1 or 2 procedure codes (with exception of 81479 x 1 only being listed once if it appropriately represents more than one gene in the panel)
  3. ALL gene tests in the panel must be listed on the request and rationale for the clinical utility for the gene test must come from the ordering provider.
  4. If ALL codes that represent the testing of the panel are not submitted, the test will be denied as not medically necessary due to incorrect coding process, as neither laboratory or clinical reviewer should assign meaning to incomplete unspecified panel codes.

Policy Guidelines 
The literature suggests that certain individuals be tested for inherited (germline) gene mutations based on family history, personal history, and increased risk based on prediction models. This information from referenced sources on various disease states (for example, hereditary cancer syndromes and inherited diseases like cystic fibrosis) serves as the basis for medical necessity criteria stated within this policy. The following sources provide ordering practitioner insight into current accepted testing practices, based on documented clinical utility, as well as material suitable for patient education regarding contemplated genetic testing.

Gene Reviews (disease-specific information) is an international point-of-care resource for clinicians, and provides clinically relevant and medically actionable information for inherited disorders. (https://www.ncbi.nlm.nih.gov/books/NBK1116/)

Eurogentest clinical utility gene cards (CUGCs) are disease-specific guidelines regarding the clinical utility of genetic testing. Clinical utility refers to the ability of a genetic test to significantly affect the clinical setting and patient outcome. CUGCs cover all elements relevant for assessing risks and benefits of genetic test application. Due to their clear and concise format, they enable quick guidance to all stakeholders, including clinicians, geneticists, referrers, service providers and payers. (http://www.eurogentest.org/index.php?id=668).

American College of Medical Genetics and Genomics provides recommendations that are designed primarily as an educational resource for medical geneticists and other healthcare providers to help them provide quality medical genetics services; they should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. (https://www.acmg.net).

Genetics Home Reference sponsored by the National Institutes of Health provides consumer-friendly information about the effects of genetic variation on human health. (https://ghr.nlm.nih.gov/).

Is also important to note this testing should be accompanied by genetic counseling from an appropriate professional to assist patients and their families in understanding implications of genetic disorders (NIH, n.d.). These testing results play into the healthcare decisions and outcomes for the member and/or the member’s family in these circumstances, making this counseling medically necessary.

References 

  1. National Cancer Institute. (n.d.). Germline mutation. Retrieved February 11, 2017, from https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=46384
  2. National Cancer Institute. n.d. The genetics of cancer. Retrieved February 2, 2017, from https://www.cancer.gov/about-cancer/causes-prevention/genetics
  3. National Institutes of Health. n.d. Cancer genetics risk assessment and counseling (PDQ®)–health professional version. Retrieved February 9, 2017, from https://www.cancer.gov/about-cancer/causes-prevention/genetics/risk-assessment-pdq#section/_5
  4. National Institute of Health. 2017. What is genetic testing? Retrieved February 1, 2017, from https://ghr.nlm.nih.gov/primer/testing/genetictesting

Coding Section 

Codes Numbers Description
CPT  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) 
  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 
  81173 (effective 01/01/2019)  AR (androgen receptor) (eg, spinal and bulbar muscular atrophy, Kennedy disease, X chromosome inactivation) gene analysis; full gene sequence 
  81174 (effective 01/01/2019)  AR (androgen receptor) (eg, spinal and bulbar muscular atrophy, Kennedy disease, X chromosome inactivation) gene analysis; known familial variant 
  81177 (effective 01/01/2019)  ATN1 (atrophin 1) (eg, dentatorubral-pallidoluysian atrophy) gene analysis, evaluation to detect abnormal (eg, expanded) alleles 
  81178 (effective 01/01/2019)  ATXN1 (ataxin 1) (eg, spinocerebellar ataxia) gene analysis, evaluation to detect abnormal (eg, expanded) alleles 
  81179 (effective 01/01/2019)  ATXN2 (ataxin 2) (eg, spinocerebellar ataxia) gene analysis, evaluation to detect abnormal (eg, expanded) alleles 
  81180 (effective 01/01/2019)  ATXN3 (ataxin 3) (eg, spinocerebellar ataxia, Machado-Joseph disease) gene analysis, evaluation to detect abnormal (eg, expanded) alleles 
  81181 (effective 01/01/2019)  ATXN7 (ataxin 7) (eg, spinocerebellar ataxia) gene analysis, evaluation to detect abnormal (eg, expanded) alleles 
  81182 (effective 01/01/2019)  ATXN8OS (ATXN8 opposite strand [non-protein coding]) (eg, spinocerebellar ataxia) gene analysis, evaluation to detect abnormal (eg, expanded) alleles 
  81183 (effective 01/01/2019)  ATXN10 (ataxin 10) (eg, spinocerebellar ataxia) gene analysis, evaluation to detect abnormal (eg, expanded) alleles 
  81187 (effective 01/01/2019)  CNBP (CCHC-type zinc finger nucleic acid binding protein) (eg, myotonic dystrophy type 2) gene analysis, evaluation to detect abnormal (eg, expanded) alleles 
  81188 (effective 01/01/2019)  CSTB (cystatin B) (eg, Unverricht-Lundborg disease) gene analysis; evaluation to detect abnormal (eg, expanded) alleles 
  81189 (effective 01/01/2019)  CSTB (cystatin B) (eg, Unverricht-Lundborg disease) gene analysis; full gene sequence 
  81190 (effective 01/01/2019)   CSTB (cystatin B) (eg, Unverricht-Lundborg disease) gene analysis; known familial variant(s) 
  81204 (effective 01/01/2019)  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) 
  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 
  81233 (effective 01/01/2019)  BTK (Bruton's tyrosine kinase) (eg, chronic lymphocytic leukemia) gene analysis, common variants (eg, C481S, C481R, C481F) 
  81234 (effective 01/01/2019)  DMPK (DM1 protein kinase) (eg, myotonic dystrophy type 1) gene analysis; evaluation to detect abnormal (expanded) alleles 
  81236 (effective 01/01/2019)  EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) (eg, myelodysplastic syndrome, myeloproliferative neoplasms) gene analysis, full gene sequence 
  81237 (effective 01/01/2019)  EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) (eg, diffuse large B-cell lymphoma) gene analysis, common variant(s) (eg, codon 646) 
  81238 (effective 1/1/2018) F9 (coagulation factor IX) (eg, hemophilia B), full gene sequence 
  81239 (effective 01/01/2019)  DMPK (DM1 protein kinase) (eg, myotonic dystrophy type 1) gene analysis; characterization of alleles (eg, expanded size) 
  81247 (effective 1/1/2018) G6PD (glucose-6-phosphate dehydrogenase) (eg, hemolytic anemia, jaundice), gene analysis; common variant(s) (eg, A, A-) 
  81248 (effective 1/1/2018)  G6PD (glucose-6-phosphate dehydrogenase) (eg, hemolytic anemia, jaundice), gene analysis; known familial variant(s) 
  81249 (effective 1/1/2018) G6PD (glucose-6-phosphate dehydrogenase) (eg, hemolytic anemia, jaundice), gene analysis; full gene sequence 
  81252 GJB2 (gap junction protein, beta 2, 26kDa, connexin 26) (eg, nonsyndromic hearing loss) 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) 
  81271 (effective 01/01/2019)  HTT (huntingtin) (eg, Huntington disease) gene analysis; evaluation to detect abnormal (eg, expanded) alleles 
  81274 (effective 01/01/2019)  HTT (huntingtin) (eg, Huntington disease) gene analysis; characterization of alleles (eg, expanded size) 
  81283 (effective 1/1/2018) IFNL3 (interferon, lambda 3) (eg, drug response), gene analysis, rs12979860 variant 
  81284 (effective 01/01/2019)  FXN (frataxin) (eg, Friedreich ataxia) gene analysis; evaluation to detect abnormal (expanded) alleles 
  81285 (effective 01/01/2019)  FXN (frataxin) (eg, Friedreich ataxia) gene analysis; characterization of alleles (eg, expanded size) 
  81286 (effective 01/01/2019)  FXN (frataxin) (eg, Friedreich ataxia) gene analysis; full gene sequence 
  81289 (effective 01/01/2019)  FXN (frataxin) (eg, Friedreich ataxia) gene analysis; known familial variant(s) 
  81305 (effective 01/01/2019)  MYD88 (myeloid differentiation primary response 88) (eg, Waldenstrom's macroglobulinemia, lymphoplasmacytic leukemia) gene analysis, p.Leu265Pro (L265P) variant 
  81307 (effective 01/01/2020) 

PALB2 (partner and localizer of BRCA2) (eg, breast and pancreatic cancer) gene analysis; full gene sequence

  81308 (effective 01/01/2020)  

Known familial variant

  81309 (effective 01/01/2020)   

PIK3CA (phosphatidylinositol-4, 5-biphosphate 3-kinase, catalytic subunit alpha) (eg, colorectal and breast cancer) gene analysis, targeted sequence analysis (eg, exons 7, 9, 20)

  81312 (effective 01/01/2019)  PABPN1 (poly[A] binding protein nuclear 1) (eg, oculopharyngeal muscular dystrophy) gene analysis, evaluation to detect abnormal (eg, expanded) alleles 
  81320 (effective 01/01/2019)   PLCG2 (phospholipase C gamma 2) (eg, chronic lymphocytic leukemia) gene analysis, common variants (eg, R665W, S707F, L845F) 
  81329 (effective 01/01/2019)  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 
  81333 (effective 01/01/2019)  TGFBI (transforming growth factor beta-induced) (eg, corneal dystrophy) gene analysis, common variants (eg, R124H, R124C, R124L, R555W, R555Q) 
  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 (effective 01/01/2019)  PPP2R2B (protein phosphatase 2 regulatory subunit Bbeta) (eg, spinocerebellar ataxia) gene analysis, evaluation to detect abnormal (eg, expanded) alleles 
  81344 (effective 01/01/2019)  TBP (TATA box binding protein) (eg, spinocerebellar ataxia) gene analysis, evaluation to detect abnormal (eg, expanded) alleles 
  81361 (effective 1/1/2018) HBB (hemoglobin, subunit beta) (eg, sickle cell anemia, beta thalassemia, hemoglobinopathy); common variant(s) (eg, HbS, HbC, HbE) 
  81362 (effective 1/1/2018) HBB (hemoglobin, subunit beta) (eg, sickle cell anemia, beta thalassemia, hemoglobinopathy); known familial variant(s) 
  81363 (effective 1/1/2018) HBB (hemoglobin, subunit beta) (eg, sickle cell anemia, beta thalassemia, hemoglobinopathy); duplication/deletion variant(s) 
  81364 (effective 1/1/2018) HBB (hemoglobin, subunit beta) (eg, sickle cell anemia, beta thalassemia, hemoglobinopathy); full gene sequence 
  81400

 Molecular pathology procedure, Level 1

Genes: ACADM, ACE, AGTR1, BCKDHA, CCR5, CLRN1, DPYD, F2, F5, F7, F13B, FGB, FGFR1, FGFR3, FKTN, GNE, Human Platelet Antigen 1 genotyping, Human Platelet Antigen 2 genotyping, Human Platelet Antigen 3 genotyping, Human Platelet Antigen 4 genotyping, Human Platelet Antigen 5 genotyping, Human Platelet Antigen 6 genotyping, Human Platelet Antigen 9 genotyping, Human Platelet Antigen 15 genotyping, IL28B, IVD, LCT, NEB, PCDH15, SERPINE1, SHOC2, SMN1, SRY, TOR1A 
  81401

Molecular pathology procedure, Level 2 (eg, 2-10 SNPs, 1 methylated variant, or 1 somatic variant [typically using nonsequencing target variant analysis], or detection of a dynamic mutation disorder/triplet repeat)

Genes: ABCC8, ABL1, ACADM, ADRB2, AFF2, APOB, APOE, AR, ATN1, ATXN1, ATXN2, ATXN3, ATXN7, ATXN8OS, ATXN10, CACNA1A, CBFB/MYH11, CBS, CCND1/IGH, CFH/ARMS2, CNBP, CSTB, CYP3A4, CYP3A5, DEK/NUP214, DMPK, E2A/PBX1, EML4/ALK, ETV6/NTRK3, ETV6/RUNX1, EWSR1/ATF1, EWSR1/ERG, EWSR1/FLI1, EWSR1/WT1, F11, FIP1L1/PDGFRA, FLG,FOXO1/PAX3, FOXO1/PAX7, FUS/DDIT3, FXN, GALC, GALT, H19, HBB, HTT, IGH@/BCL2 (When both MBR and mcr breakpoints are performed, use 81402), KCNQ1OT1, LRRK2, MED12, MEG3/DLK1, MLL/AFF1, MLL/MLLT3, MT-ATP6, MT-ND4, MT-ND5,MT-RNR1, MT-TK, MT-TL1, MT-TS1, MT-RNR1, MUTYH, NOD2, NPM1/ALK, PABPN1, PAX8/PPARG, PPP2R2B, PRSS1, PYGM, RUNX1/RUNX1T1, SMN1/SMN2 (For duplication/deletion analysis of MN1/SMN2, use 81401)SS18/SSX1, SS18/SSX2, TBP, TPMT, TYMS, VWF 
  81402

 Molecular pathology procedure, Level 3

Genes: Chromosome 1p-/19q-, Chromosome 18q, COL1A1/PDGFB, CYP21A2, ESR1/PGR, IGH@/BCL2, MEFV, MPL, TRD@, Uniparental disomy (UPD) 
  81403

Molecular pathology procedure, Level 4

Genes: ANG, ARX, CEL, CTNNB1, DAZ/SRY, DNMT3A, EPCAM, F8, F12, FGFR3 (For targeted sequence analysis of multiple FGFR3 exons, use 81404), GJB1, GNAQ, HBB,Human erythrocyte antigen gene analyses, HRAS, IDH1, IDH2, JAK2, Killer cell immunoglobulin-like receptor (KIR) gene family, Known familial variant not otherwise specified, for gene listed in Tier 1 or Tier 2, or identified during a genomic sequencing procedure, DNA sequence analysis, each variant exon (For a known familial variant that is considered a common variant, use specific common variant Tier 1 or Tier 2 code), KCNC3, KCNJ2, CNJ11, MC4R,MICA, MPL, MT-RNR1, MT-TS1, NDP, NHLRC1, PHOX2B,PLN, RHD (For human erythrocyte gene analysis of RHD, use a separate unit of 81403), SH2D1A, SMN1, TWIST1, UBA1, VHL, VWF 
  81404

Molecular pathology procedure, Level 5

Genes: ACADS, AFF2, AQP2, ARX, AVPR2, BBS10, BTD, C10orf2, CAV3, CD40LG, CDKN2A, CLRN1, COX6B1, CPT2, CRX, CSTB, CYP1B1, DMPK, GR2, EPM2A, FGF23, FGFR2, FGFR3,FHL1, FKRP, FOXG1, FSHMD1A, FSHMD1A, FXN, GP1BB, HBA1/HBA2 (For common deletion variants of alpha globin 1 and alpha globin 2 genes, use 81257), HBB, HNF1B, HRAS, HSD3B2, HSD11B2, HSPB1, KCNJ1, KCNJ10, LITAF, MEFV, MEN1, MMACHC, MPV17, NDUFA1, NDUFAF2, NDUFS4, NIPA1, NLGN4X, NPC2, PDX1, PHOX2B, PIK3CA, PLP1, PQBP1, PROP1, PRPH2, PRSS1, RAF1, RET,RHO, SCN1B, SCO2, SDHC, SDHD, SGCG, SH2D1A, SLC16A2, SLC25A20, SLC25A4, SOD1, SPINK1, STK11, TACO1, THAP1, TOR1A, TP53, TTPA, TTR, TWIST1, TYR, USH1G, VHL, VWF, ZEB2, ZNF41 
  81405

Molecular pathology procedure, Level 6

Genes:  ABCD1, ACTA2, ACTC1, ANKRD1, APTX, ARSA, BCKDHA, BCS1L, BMPR2, CASQ2, CASR, CDKL5, CHRNA4, CHRNB2, COX10, COX15, CYP11B1, CYP17A1, Cytogenomic constitutional targeted microarray analysis of chromosome 22q13 by interrogation of genomic regions for copy number and single nucleotide polymorphism (SNP) variants for chromosomal abnormalities, CYP21A2, DBT, DCX, DFNB59, DGUOK, DHCR7, EIF2B2, EMD, ENG, EYA1, F9, GFR1, FKTN, FTSJ1, GABRG2, GCH1, GDAP1, GFAP, GHR, GHRHR, GLA, HBA1/HBA2, HNF1A, HNF1B, HTRA1, IDS, IL2RG, ISPD, KRAS, LAMP2, LDLR, MEN1, MMAA, MMAB, MPI, MPV17, MPZ, MTM1, MYL2, MYL3, MYOT, NDUFS7, NDUFS8, NDUFV1, NEFL, NF2, NLGN3, NLGN4X, NPHS2, NSD1, OTC, PAFAH1B1, PARK2, PCCA, PCDH19, PDHA1, PDHB, PINK1, PLP1, POU1F1, PRX, PQBP1, PSEN1, RAB7A, RAI1, REEP1, RET, RPS19, RRM2B, SCO1, SDHB, SDHC, SGCA, SGCB, SGCD, SGCE, SGCG, SHOC2, SIL1, SLC2A1, SLC16A2, SLC22A5, SLC25A20, SMAD4,SMN1, SPAST, SPRED, STAT3, STK11, SURF1, TARDBP, TBX5, TCF4, TGFBR1, THRB, TK2, TNNC1, TNNI3, TP53, TPM1, TSC1, TYMP, VWF, WT1, ZEB2 
  81406

Molecular pathology procedure, Level 7

Genes:  ACADVL, ACTN4, AFG3L2, AIRE, ALDH7A1, ANO5, APP, ASS1, ATL1, ATP1A2, ATP7B, BBS1, BBS2, BCKDHB, BEST1, BMPR2, BRAF,BSCL2, BTK, CACNB2, CAPN3, CBS, CDH1, CDKL5, CLCN1, CLCNKB, CNTNAP2, COL6A2, CPT1A, CRB1, CREBBP, Cytogenomic microarray analysis, neoplasia, DBT, DLAT, DLD, DSC2, DSG2, DSP, EFHC1, EIF2B3, EIF2B4, EIF2B5, ENG, EYA1, F8, FAH, FASTKD2, FIG4, FTSJ1, FUS, GAA, GALC, GALT, GARS, GCDH, GCK, GLUD1, GNE, GRN, HADHA, HADHB, HEXA, HLCS, HNF4A, IDUA, INF2, IVD, JAG1, JUP, KAL1, KCNH2, KCNQ1, KCNQ2, LDB3, LDLR, LEPR, LHCGR, LMNA, LRP5, MAP2K1, MAP2K2, MAPT, MCCC1, MCCC2, MFN2, MTM1, MUT, MUTYH, NDUFS1, NF2, NOTCH3, NPC1, NPHP1, NSD1, OPA1, OPTN, PAFAH1B1, PAH, PALB2, PARK2, PAX2, PC, PCCA, PCCB, PCDH15, PCSK9, PDHA1, PDHX, PHEX, PKD2, PKP2, PNKD, POLG, POMGNT1, POMT1, POMT2, PRKAG2, PRKCG, PSEN2, PTPN11, PYGM, RAF1, RET, RPE65, RYR1, SCN4A, SCNN1A, SCNN1B, SCNN1G, SDHA, SETX, SGCE, SH3TC2, SLC9A6, SLC26A4, SLC37A4, SMAD4, SOS1, SPAST, SPG7, STXBP1, TAZ, TCF4, TH, TMEM43, TNNT2, TRPC6, TSC1, TSC2, UBE3A, UMOD, VWF, WAS 
  81407

Molecular pathology procedure, Level 8

Genes:  ABCC8, AGL, AHI1, ASPM, CACNA1A, CHD7, COL4A4, COL4A5, COL6A1, COL6A2, COL6A3, CREBBP, F8, JAG1, KDM5C, KIAA0196, L1CAM, LAMB2, MYBPC3, MYH6, MYH7, MYO7A, NOTCH1, NPHS1, OPA1, PCDH15, PKD1, PLCE1, SCN1A, SCN5A, SLC12A1, SLC12A3, SPG11, PTBN2, TMEM67, TSC2, USH1C, VPS13B, WDR62 
  81408

Molecular pathology procedure, Level 9

Genes:  ABCA4, ATM, CDH23, CEP290, COL1A1, COL1A2, COL4A1, COL4A3, COL4A5, DMD, DYSF, FBN1, ITPR1, LAMA2, LRRK2, MYH11, NEB, NF1, PKHD1, RYR1, RYR2, USH2A, VPS13B, VWF 
  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 (effective 01/01/2019) 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, ASPA, ATP7B, BCKDHA, BCKDHB, BLM, CFTR, DHCR7, FANCC, G6PC, GAA, GALT, GBA, GBE1, HBB, HEXA, IKBKAP, MCOLN1, PAH) 
  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 (only 1 unit of service) 
  96040 Medical genetics & genetic counseling services 
HCPCS G0452 Molecular pathology procedure; physician interpretation and report 
  S0265 Genetic counseling, under physician supervision, each 15 minutes
  S3840 DNA analysis for germline mutations 
ICD-10 CM All Z codes Family history malignancy 
  Z84.81 Family history genetic disease carrier 
  Z13.71 Screening for genetic disease carrier status

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each Policy. They may not be all-inclusive. 

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross and Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

"Current Procedural Terminology © American Medical Association.  All Rights Reserved" 

History From 2017 Forward     

01/06/2020 

Interim review to update coding. No other changes made. 

12/13/2019 

Added codes 81227, 81307, 81308 and 81309.

07/16/2019 

Updating the coding section with codes 81336 and 81337. No other changes. 

07/01/2019 

Interim review. Adding Reimbursement section to policy. 

05/10/2019

Updating verbiage regarding genetic counseling for specificity.. 

04/03/2019 

Annual review, adding policy statement #3 regarding germline multi gene panel testing. No other changes to policy intent. Also updating coding. 

12/21/2018 

Updated with additional 2019 codes.  

12/18/2018 

Updating policy with 2019 codes. 

04/28/2018 

Annual review. updating cpt coding. no change to policy intent. 

12/7/2017 

Updating policy with 2018 coding. No other changes.

04/24/2017 

Updating Category to Laboratory. 

04/06/2017

New Policy

 


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