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A.2.04.93
Commercially available cancer susceptibility gene panels can test for multiple variants associated with a specific type of cancer or can include variants associated with a wide variety of cancers. Some of these variants are associated with inherited cancer syndromes. The cancer type(s), as well as a cancer history involving multiple family members, increase the clinical concern for the presence of a heritable genetic variant. It has been proposed that variant testing using next-generation sequencing technology to analyze multiple genes at once (panel testing) can optimize genetic testing in these individuals compared with sequencing single genes.
Genetic Testing for Cancer Susceptibility
Genetic testing for cancer susceptibility may be approached by a focused method that involves testing for gene(s) that may be the cause of the heritable or familial cancer. Panel testing with next-generation sequencing involves evaluating sequence variants in multiple genes at once.
Multiple commercial companies and medical center laboratories offer genetic testing panels that use next-generation sequencing (NGS) methods for hereditary cancers. Next-generation sequencing is one of several methods that use massively parallel platforms to allow the sequencing of large stretches of DNA. Panel testing is potentially associated with greater efficiencies in the evaluation of genetic diseases; however, it may provide information on genetic variants of uncertain clinical significance or findings that would not lead to changes in patient management.
Genes Included in Next-Generation Sequencing Panels
The following summarizes the function and disease association of major genes included in NGS panels. This summary is not comprehensive.
BRCA1 and BRCA2VariantsBRCA1 and BRCA2 germline variants are associated with hereditary breast and ovarian cancer syndrome, which is associated most strongly with increased susceptibility to breast cancer at an early age, bilateral breast cancer, male breast cancer, ovarian cancer, cancer of the fallopian tube, and primary peritoneal cancer. BRCA1 and BCRA2 variants are also associated with increased risk of other cancers, including prostate cancer, pancreatic cancer, gastrointestinal cancers, melanoma, and laryngeal cancer.
APC VariantsAPC germline variants are associated with familial adenomatous polyposis (FAP) and attenuated FAP. Familial adenomatous polyposis is an autosomal dominant colon cancer predisposition syndrome characterized by hundreds to thousands of colorectal adenomatous polyps and accounts for about 1% of all colorectal cancers (CRCs).
ATM VariantsATM is associated with the autosomal recessive condition ataxia-telangiectasia. This condition is characterized by progressive cerebellar ataxia with onset between the ages of 1 and 4 years, telangiectasias of the conjunctivae, oculomotor apraxia, immune defects, and cancer predisposition, particularly leukemia and lymphoma.
BARD1, BRIP1, MRE11A, NBN, RAD50, and RAD51C VariantsBARD1, BRIP1, MRE11A, NBN, RAD50, and RAD51C are genes in the Fanconi anemia/BRCA pathway. Variants in these genes are estimated to confer up to a 4-fold increase in the risk for breast cancer. This pathway is also associated with a higher risk of ovarian cancer, and less often, pancreatic cancer.
BMPR1A and SMAD4 VariantsBMPR1A and SMAD4 are genes mutated in juvenile polyposis syndrome and account for 45% to 60% of cases. Juvenile polyposis syndrome is an autosomal dominant disorder that predisposes to the development of polyps in the gastrointestinal tract. Malignant transformation can occur, and the risk of gastrointestinal cancer has been estimated from 9% to 50%.
CHEK2 VariantsCHEK2 gene variants confer an increased risk of developing several different types of cancer, including breast, prostate, colon, thyroid, and kidney. CHEK2 regulates the function of BRCA1 protein in DNA repair and has been associated with familial breast cancers.
CDH1 VariantsCDH1 is a tumor suppressing gene located on chromosome 16q22.1 that encodes the cell-to-cell adhesion protein E-cadherin. Germline variants in the CDH1 gene have been associated with an increased risk of developing hereditary diffuse gastric cancer (DGC) and lobular breast cancer. A diagnosis of HDGC can be confirmed by genetic testing, although 20% to 40% of families with suspected HDGC do not have a CDH1 variant on genetic testing. Pathogenic CDH1 variants have been described in Maori families in New Zealand, and individuals of Maori ethnicity have a higher prevalence of diffuse-type gastric cancer than non-Maori New Zealanders. The estimated cumulative risk of gastric cancer for CDH1 variant carriers by age 80 years is 70% for men and 56% for women. CDH1 variants are associated with a lifetime risk of 39% to 52% of lobular breast cancer.
EPCAM, MLH1, MSH2, MSH6 and PMS2 VariantsEPCAM, MLH1, MSH2, MSH6 and PMS2 are mismatch repair genes associated with Lynch syndrome (hereditary nonpolyposis colorectal cancer). Lynch syndrome is estimated to cause 2% to 5% of all colon cancers. Lynch syndrome is associated with a significantly increased risk of several types of cancer: colon cancer (60% to 80% lifetime risk), uterine/endometrial cancer (20% to 60% lifetime risk), gastric cancer (11% to 19% lifetime risk), and ovarian cancer (4% to 13% lifetime risk). The risks of other types of cancer, including the small intestine, hepatobiliary tract, upper urinary tract, and brain, are also elevated.
MUTYH VariantsMUTYH germline variants are associated with an autosomal recessive form of hereditary polyposis. It has been reported that 33% and 57% of patients with clinical FAP and attenuated FAP, respectively, who are negative for variants in the APC gene, have MUTYH variants.
PALB2 VariantsPALB2 germline variants are associated with an increased risk of pancreatic and breast cancer. Familial pancreatic and/or breast cancer due to PALB2 variants are inherited in an autosomal dominant pattern.
PTEN VariantsPTEN variants are associated with PTEN hamartoma tumor syndrome (PHTS), which includes Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome, and Proteus syndrome. Cowden syndrome is characterized by a high risk of developing tumors of the thyroid, breast, and endometrium. Affected persons have a lifetime risk of up to 50% for breast cancer, 10% for thyroid cancer, and 5% to 10% for endometrial cancer.
STK11 VariantsSTK11 germline variants are associated with Peutz-Jeghers syndrome, an autosomal dominant disorder, with a 57% to 81% risk of developing cancer by age 70, of which gastrointestinal and breast cancers are the most common.
TP53 VariantsTP53 are associated with Li-Fraumeni syndrome. People with TP53 variants have a 50% risk of developing any of the associated cancers by age 30 and a lifetime risk up to 90%, including sarcomas, breast cancer, brain tumors, and adrenal gland cancers.
NF1 VariantsThe NF1 gene encodes a negative regulator in the ras signal transduction pathway. Variants in the NF1 gene have been associated with neurofibromatosis type 1, juvenile myelomonocytic leukemia, and Watson syndrome.
RAD51D VariantsRAD51D germline variants are associated with familial breast and ovarian cancers.
CDK4 VariantsCDK4 (cyclin-dependent kinase-4) is a protein-serine kinase involved in cell cycle regulation. Variants in the CDK4 gene are associated with a variety of cancers, particularly cutaneous melanoma.
CDKN2A VariantsThe CDKN2A (cyclin-dependent kinase inhibitor 2A) gene encodes proteins that act as multiple tumor suppressors through their involvement in 2 cell cycle regulatory pathways: the p53 pathway and the RB1 pathway. Variants or deletions in CDKN2A are frequently found in multiple types of tumor cells. Germline variants in CDKN2A have been associated with the risk of melanoma, along with pancreatic and central nervous system cancers.
RET VariantsRET encodes a receptor tyrosine kinase; variants in this gene are associated with multiple endocrine neoplasia syndromes (types IIA and IIB) and medullary thyroid carcinoma.
SDHA, SDHB, SDHC, SDHD, and SDHAF2VariantsSDHA, SDHB, SDHC, SDHD, and SDHAF2 gene products are involved in the assembly and function of a component of the mitochondrial respiratory chain. Germline variants in these genes are associated with the development of paragangliomas, pheochromocytomas, gastrointestinal stromal tumors, and a PTEN-negative Cowden-like syndrome.
TMEM127 VariantsTMEM127 (transmembrane protein 127) germline variants are associated with the risk of pheochromocytomas.
VHL VariantsVHL germline variants are associated with Hippel-Lindau syndrome, an autosomal dominant familial cancer syndrome. This syndrome is associated with various malignant and benign tumors, including central nervous system tumors, renal cancers, pheochromocytomas, and pancreatic neuroendocrine tumors.
FH VariantsFH (fumarate hydratase) variants are associated with renal cell and uterine cancers.
FLCN VariantsFLCN (folliculin) acts as a tumor suppressor gene; variants in this gene are associated with the autosomal dominant Birt-Hogg-Dube syndrome, which is characterized by hair follicle hamartomas, kidney tumors, and colorectal cancer.
MET VariantsMET is a proto-oncogene that acts as the hepatocyte growth factor receptor. MET variants are associated with hepatocellular carcinoma and papillary renal cell carcinoma.
MITF VariantsMicrophthalmia-associated transcription factor (encoded by the MITF gene) is a transcription factor involved in melanocyte differentiation. MITF variants lead to several auditory-pigmentary syndromes, including Waardenburg syndrome type 2 and Tietze syndrome. MITF variants are also associated with melanoma and renal cell carcinoma.
TSC1 VariantsTSC1 (tuberous sclerosis 1) and TSC2 (tuberous sclerosis 2) encode the proteins hamartin and tuberin, which are involved in cell growth, differentiation, and proliferation. Variants in these genes are associated with the development of tuberous sclerosis complex, an autosomal dominant syndrome characterized by skin abnormalities, developmental delay, seizures, and multiple types of cancers, including central nervous system tumors, renal tumors (including angiomyolipomas, renal cell carcinomas), and cardiac rhabdomyomas.
XRCC2 VariantsXRCC2 encodes proteins thought to be related to the RAD51 protein product that is involved in DNA double-stranded breaks. Variants may be associated with Fanconi anemia and breast cancer.
FANCCVariantsFANCC (Fanconi-anemia complementation group C) is one of several DNA repair genes that mutate in Fanconi anemia, which is characterized by bone marrow failure and a high predisposition to multiple types of cancer.
AXIN2 VariantsAXIN2 variants are associated with familial adenomatous polyposis syndrome, although the phenotypes associated with AXIN2 variants do not appear to be well-characterized.
Hereditary Cancer and Cancer Syndromes
Genetic testing for breast and ovarian cancer syndromes are reviewed in the Germline Genetic Testing for Hereditary Breast/Ovarian Cancer Syndrome and Other High-Risk Cancers (BRCA1, BRCA2, PALB2) , Use of Common Genetic Variants (Single Nucleotide Variants) to Predict Risk of Nonfamilial Breast Cancer) , Germline Genetic Testing for Gene Variants Associated with Breast Cancer in Individuals at High Breast Cancer Risk (CHEK2, ATM, and BARD1) , and Molecular Testing for Germline Variants Associated with Ovarian Cancer (BRIP1, RAD51C, RAD51D, NBN) medical policies.
Genetic testing for Li-Fraumeni syndrome is reviewed in the Genetic Testing for Li-Fraumeni Syndrome medical policy.
Cowden Syndrome is a part of PHTS and is the only PHTS disorder associated with a documented predisposition to malignancies. Genetic testing for CS is evaluated in the Genetic Testing for PTEN Hamartoma Tumor Syndrome medical policy.
Genetic testing for hereditary colon cancer syndromes are addressed in the Genetic Testing for Lynch Syndrome and Other Inherited Colon Cancer Syndromes medical policy.
Genetic testing for familial pancreatic testing is evaluated in the Germline Genetic Testing for Pancreatic Cancer Susceptibility Genes (ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, STK11, and TP53) medical policy.
Genetic testing for hereditary DGC is evaluated in the Germline Genetic Testing for Hereditary Diffuse Gastric Cancer (CDH1, CTNNA1) medical policy.
Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests (LDTs) must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments (CLIA). Laboratories that offer LDTs must be licensed by the CLIA for high-complexity testing. To date, the U.S. Food and Drug Administration has chosen not to require any regulatory review of these tests.
General genetic cancer susceptibility panel testing is considered investigational; however, when the coverage criteria of other policies is met (see related policies), then limited genetic cancer susceptibility panels including only the gene variants for which a given member qualifies may be considered medically necessary.
None
The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
Although genetic cancer susceptibility panel testing is considered investigational, there may be individual components of the panel that are medically necessary. Refer to the Genetic Testing medical policy.
Genetics Nomenclature Update
The Human Genome Variation Society nomenclature is used to report information on variants found in DNA and serves as an international standard in DNA diagnostics. It is being implemented for genetic testing medical evidence review updates starting in 2017 (see Table 1). The Society’s nomenclature is recommended by the Human Variome Project, the Human Genome Organization, and by the Human Genome Variation Society itself.
The American College of Medical Genetics and Genomics and the Association for Molecular Pathology standards and guidelines for interpretation of sequence variants represent expert opinion from both organizations, in addition to the College of American Pathologists. These recommendations primarily apply to genetic tests used in clinical laboratories, including genotyping, single genes, panels, exomes, and genomes. Table 2 shows the recommended standard terminology—“pathogenic,” “likely pathogenic,” “uncertain significance,” “likely benign,” and “benign”—to describe variants identified that cause Mendelian disorders.
Table 1. Nomenclature to Report on Variants Found in DNA
Previous | Updated | Definition |
Mutation | Disease-associated variant | Disease-associated change in the DNA sequence |
Variant | Change in the DNA sequence | |
Familial variant | Disease-associated variant identified in a proband for use in subsequent targeted genetic testing in first-degree relatives |
Table 2. ACMG-AMP Standards and Guidelines for Variant Classification
Variant Classification | Definition |
Pathogenic | Disease-causing change in the DNA sequence |
Likely pathogenic | Likely disease-causing change in the DNA sequence |
Variant of uncertain significance | Change in DNA sequence with uncertain effects on disease |
Likely benign | Likely benign change in the DNA sequence |
Benign | Benign change in the DNA sequence |
Genetic Counseling
Genetic counseling is primarily aimed at individuals who are at risk for inherited disorders, and experts recommend formal genetic counseling in most cases when genetic testing for an inherited condition is considered. The interpretation of the results of genetic tests and the understanding of risk factors can be very difficult and complex. Therefore, genetic counseling will assist individuals in understanding the possible benefits and harms of genetic testing, including the possible impact of the information on the individual's family. Genetic counseling may alter the utilization of genetic testing substantially and may reduce inappropriate testing. Genetic counseling should be performed by an individual with experience and expertise in genetic medicine and genetic testing methods.
Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:
consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and
appropriate with regard to standards of good medical practice; and
not solely for the convenience of the Member, his or her Provider; and
the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.
For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.
Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.
04/01/2014: Approved by Medical Policy Advisory Committee.
07/30/2015: Code Reference section updated for ICD-10.
12/31/2015: Policy description updated regarding next-generation sequencing cancer panels and the genes associated with those panels. Policy statement unchanged. Policy guidelines updated to state that although genetic cancer susceptibility panels using next-generation sequencing are considered investigational, there may be individual components of the panel that are medically necessary. Added link to Genetic Testing medical policy. Investigative definition updated. Code Reference section updated to add new 2016 CPT codes 81412, 81432, 81433, 81434, 81437, 81438, and 81442.
04/01/2016: Code Reference section updated to add CPT codes 81445, 81450, and 81455 as investigational.
06/07/2016: Policy number A.2.04.93 added.
08/18/2016: Policy description updated regarding laboratory-developed tests. Policy statement unchanged.
08/01/2017: Code Reference section updated to add new CPT codes 0008U, 0012U, 0013U, 0014U, and 0017U.
12/11/2017: Policy description updated regarding next-generation sequencing cancer panels and hereditary diffuse gastric cancer. Policy statement unchanged. Policy Guidelines updated to add the genetics nomenclature update and genetic counseling information.
12/21/2017: Code Reference sections updated to add new 2018 CPT codes 81120 and 81121. Revised description for CPT code 81432 effective 01/01/2018. Removed CPT code 81434.
03/27/2018: Code Reference section updated to add new CPT code 0037U, effective 04/01/2018.
06/21/2018: Code Reference section updated to add CPT code 0022U and new codes 0048U, 0050U, 0056U, and 0057U, effective 07/01/2018.
10/29/2018: Policy description extensively revised. Removed tables with hereditary cancer test panels; added information regarding hereditary diffuse gastric cancer and hereditary colon cancer syndromes. Policy statement unchanged.
12/19/2018: Code Reference section updated to add new CPT code 81443, effective 01/01/2019.
07/01/2019: Code Reference section updated to add new CPT codes 0101U, 0102U, 0103U, and 0104U.
09/17/2019: Code Reference section updated to add new CPT codes 0120U, 0129U, 0130U, 0131U, 0132U, 0134U, 0135U, 0136U, 0137U, and 0138U, effective 10/01/2019.
12/20/2019: Code Reference section updated to revise description for CPT code 0008U effective 01/01/2020.
01/03/2020: Policy reviewed. Policy statement revised for clarity to state that genetic cancer susceptibility panel testing is considered investigational. It previously stated: Genetic cancer susceptibility panels using next-generation sequencing are considered investigational. Policy Guidelines updated regarding genetic cancer susceptibility panel testing.
03/17/2020: Code Reference section updated to add new CPT code 0171U, effective 04/01/2020.
06/26/2020: Code Reference section updated to add new CPT code 0179U, effective 07/01/2020.
09/22/2020: Code Reference section updated to add new CPT code 0211U, effective 10/01/2020. Removed deleted CPT code 0057U.
12/17/2020: Code Reference section updated to add new CPT code 0239U, effective 01/01/2021. Removed deleted CPT code 0104U.
03/25/2021: Code Reference section updated to add new CPT code 0242U, effective 04/01/2021.
04/12/2021: Policy description updated regarding genetic testing for cancer susceptibility and to add related policies regarding hereditary cancer and cancer syndromes. Policy statement revised to state that general genetic cancer susceptibility panel testing is considered investigational; however, when the coverage criteria of other policies is met (see related policies), then limited genetic cancer susceptibility panels including only the gene variants for which a given member qualifies may be considered medically necessary. Policy Guidelines updated to define medically necessary.
01/14/2022: Policy description updated regarding hereditary diffuse gastric cancer. Policy statement unchanged. Policy Guidelines updated regarding genetic counseling.
03/28/2022: Code Reference section updated to revise code description for CPT code 0022U, effective 04/01/2022.
09/12/2022: Code Reference section updated to add new CPT code 0333U, effective 10/01/2022.
12/08/2022: Policy description updated regarding CDH1 variants. Removed the section regarding hereditary diffuse gastric cancer. Policy statement unchanged. Policy Guidelines updated.
12/21/2022: Code Reference section updated to revise the description for CPT codes 81445, 81450, and 81455, effective 01/01/2023.
03/30/2023: Code Reference section updated to revise the description for CPT code 0022U and to add new CPT codes 0368U and 0379U, effective 04/01/2023.
07/01/2023: Code Reference section updated to add new CPT codes 0387U, 0391U, 0395U, and 0400U.
09/25/2023: Code Reference section updated to add new CPT codes 0405U and 0406U, effective 10/01/2023.
11/13/2023: Policy description updated. Policy statement unchanged. Code Reference section updated to remove deleted CPT codes 0012U, 0013U, and 0014U.
12/21/2023: Code Reference section updated to add new 2024 CPT codes 81457, 81458, 81459, 81462, 81463, and 81464. Revised the code descriptions for CPT codes 81445, 81450, and 81455, effective 01/01/2024. Removed deleted CPT code 0056U.
02/15/2024: Code Reference section updated to remove CPT code 0008U as it is found on the Genetic Testing medical policy. CPT codes 0136U, 0400U, 81412, 81442, and 81443 were moved to the Carrier Screening for Genetic Diseases medical policy.
07/01/2024: Code Reference section updated to add new CPT codes 0473U and 0474U.
10/01/2024: Code Reference section updated to add new CPT code 0481U.
12/31/2024: Code Reference section updated to add revise description of CPT codes 81432 and 81437 effective 01/01/2025.
01/09/2025: Policy reviewed; no changes.
07/18/2025: Code Reference section updated to add new CPT codes 0565U and 0571U. Effective 07/01/2025.
Blue Cross and Blue Shield Association Policy #2.04.93
This may not be a comprehensive list of procedure codes applicable to this policy.
Code Number | Description |
CPT-4 | |
0017U | Oncology (hematolymphoid neoplasia), JAK2 mutation, DNA, PCR amplification of exons 12-14 and sequence analysis, blood or bone marrow, report of JAK2 mutation not detected or detected |
0022U | Targeted genomic sequence analysis panel, non-small cell lung neoplasia, DNA and RNA analysis, 23 genes, interrogation for sequence variants and rearrangements, reported as presence or absence of variants and associated therapy(ies) to consider |
0037U | Targeted genomic sequence analysis, solid organ neoplasm, DNA analysis of 324 genes, interrogation for sequence variants, gene copy number amplifications, gene rearrangements, microsatellite instability and tumor mutational burden |
0048U | Oncology (solid organ neoplasia), DNA, targeted sequencing of protein-coding exons of 468 cancer-associated genes, including interrogation for somatic mutations and microsatellite instability, matched with normal specimens, utilizing formalin-fixed paraffin-embedded tumor tissue, report of clinically significant mutation(s) |
0050U | Targeted genomic sequence analysis panel, acute myelogenous leukemia, DNA analysis, 194 genes, interrogation for sequence variants, copy number variants or rearrangements |
0101U | Hereditary colon cancer disorders (eg, Lynch syndrome, PTEN hamartoma syndrome, Cowden syndrome, familial adenomatosis polyposis), genomic sequence analysis panel utilizing a combination of NGS, Sanger, MLPA, and array CGH, with MRNA analytics to resolve variants of unknown significance when indicated (15 genes [sequencing and deletion/duplication], EPCAM and GREM1 [deletion/duplication only]) |
0102U | Hereditary breast cancer-related disorders (eg, hereditary breast cancer, hereditary ovarian cancer, hereditary endometrial cancer), genomic sequence analysis panel utilizing a combination of NGS, Sanger, MLPA, and array CGH, with MRNA analytics to resolve variants of unknown significance when indicated (17 genes [sequencing and deletion/duplication]) |
0103U | Hereditary ovarian cancer (eg, hereditary ovarian cancer, hereditary endometrial cancer), genomic sequence analysis panel utilizing a combination of NGS, Sanger, MLPA, and array CGH, with MRNA analytics to resolve variants of unknown significance when indicated (24 genes [sequencing and deletion/duplication], EPCAM [deletion/duplication only]) |
0120U | Oncology (B-cell lymphoma classification), mRNA, gene expression profiling by fluorescent probe hybridization of 58 genes (45 content and 13 housekeeping genes), formalin-fixed paraffin-embedded tissue, algorithm reported as likelihood for primary mediastinal B-cell lymphoma (PMBCL) and diffuse large B-cell lymphoma (DLBCL) with cell of origin subtyping in the latter |
0129U | Hereditary breast cancer–related disorders (eg, hereditary breast cancer, hereditary ovarian cancer, hereditary endometrial cancer), genomic sequence analysis and deletion/duplication analysis panel (ATM, BRCA1, BRCA2, CDH1, CHEK2, PALB2, PTEN, and TP53) |
0130U | Hereditary colon cancer disorders (eg, Lynch syndrome, PTEN hamartoma syndrome, Cowden syndrome, familial adenomatosis polyposis), targeted mRNA sequence analysis panel (APC, CDH1, CHEK2, MLH1, MSH2, MSH6, MUTYH, PMS2, PTEN, and TP53) (List separately in addition to code for primary procedure) |
0131U | Hereditary breast cancer–related disorders (eg, hereditary breast cancer, hereditary ovarian cancer, hereditary endometrial cancer), targeted mRNA sequence analysis panel (13 genes) (List separately in addition to code for primary procedure) |
0132U | Hereditary ovarian cancer–related disorders (eg, hereditary breast cancer, hereditary ovarian cancer, hereditary endometrial cancer), targeted mRNA sequence analysis panel (17 genes) (List separately in addition to code for primary procedure) |
0134U | Hereditary pan cancer (eg, hereditary breast and ovarian cancer, hereditary endometrial cancer, hereditary colorectal cancer), targeted mRNA sequence analysis panel (18 genes) (List separately in addition to code for primary procedure) |
0135U | Hereditary gynecological cancer (eg, hereditary breast and ovarian cancer, hereditary endometrial cancer, hereditary colorectal cancer), targeted mRNA sequence analysis panel (12 genes) (List separately in addition to code for primary procedure) |
0137U | PALB2 (partner and localizer of BRCA2) (eg, breast and pancreatic cancer) mRNA sequence analysis (List separately in addition to code for primary procedure) |
0138U | BRCA1 (BRCA1, DNA repair associated), BRCA2 (BRCA2, DNA repair associated) (eg, hereditary breast and ovarian cancer) mRNA sequence analysis (List separately in addition to code for primary procedure) |
0171U | Targeted genomic sequence analysis panel, acute myeloid leukemia, myelodysplastic syndrome, and myeloproliferative neoplasms, DNA analysis, 23 genes, interrogation for sequence variants, rearrangements and minimal residual disease, reported as presence/absence |
0179U | Oncology (non-small cell lung cancer), cell-free DNA, targeted sequence analysis of 23 genes (single nucleotide variations, insertions and deletions, fusions without prior knowledge of partner/breakpoint, copy number variations), with report of significant mutation(s) |
0211U | Oncology (pan-tumor), DNA and RNA by next-generation sequencing, utilizing formalin-fixed paraffin-embedded tissue, interpretative report for single nucleotide variants, copy number alterations, tumor mutational burden, and microsatellite instability, with therapy association |
0239U | Targeted genomic sequence analysis panel, solid organ neoplasm, cell-free DNA, analysis of 311 or more genes, interrogation for sequence variants, including substitutions, insertions, deletions, select rearrangements, and copy number variations |
0242U | Targeted genomic sequence analysis panel, solid organ neoplasm, cell free circulating DNA analysis of 55-74 genes, interrogation for sequence variants, gene copy number amplifications, and gene rearrangements |
0333U | Oncology (liver), surveillance for hepatocellular carcinoma (HCC) in high risk patients, analysis of methylation patterns on circulating cell-free DNA (cfDNA) plus measurement of serum of AFP/AFP-L3 and oncoprotein des-gammacarboxy-prothrombin (DCP), algorithm reported as normal or abnormal result |
0368U | Oncology (colorectal cancer), evaluation for mutations of APC, BRAF, CTNNB1, KRAS, NRAS, PIK3CA, SMAD4, and TP53, and methylation markers (MYO1G, KCNQ5, C9ORF50, FLI1, CLIP4, ZNF132 and TWIST1), multiplex quantitative polymerase chain reaction (qPCR), circulating cell-free DNA (cfDNA), plasma, report of risk score for advanced adenoma or colorectal cancer |
0379U | Targeted genomic sequence analysis panel, solid organ neoplasm, DNA (523 genes) and RNA (55 genes) by next-generation sequencing, interrogation for sequence variants, gene copy number amplifications, gene rearrangements, microsatellite instability, and tumor mutational burden |
0387U | Oncology (melanoma), autophagy and beclin 1 regulator 1 (AMBRA1) and loricrin (AMLo) by immunohistochemistry, formalin-fixed paraffin-embedded (FFPE) tissue, report for risk of progression |
0391U | Oncology (solid tumor), DNA and RNA by next-generation sequencing, utilizing formalin-fixed paraffin-embedded (FFPE) tissue, 437 genes, interpretive report for single nucleotide variants, splice-site variants, insertions/deletions, copy number alterations, gene fusions, tumor mutational burden, and microsatellite instability, with algorithm quantifying immunotherapy response score |
0395U | Oncology (lung), multi-omics (microbial DNA by shotgun next-generation sequencing and carcinoembryonic antigen and osteopontin by immunoassay), plasma, algorithm reported as malignancy risk for lung nodules in early-stage disease |
0405U | Oncology (pancreatic), 59 methylation haplotype block markers, next-generation sequencing, plasma, reported as cancer signal detected or not detected |
0406U | Oncology (lung), flow cytometry, sputum, 5 markers (meso-tetra [4-carboxyphenyl] porphyrin [TCPP], CD206, CD66b, CD3, CD19), algorithm reported as likelihood of lung cancer |
0473U | Oncology (solid tumor), next-generation sequencing (NGS) of DNA from formalin-fixed paraffin-embedded (FFPE) tissue with comparative sequence analysis from a matched normal specimen (blood or saliva), 648 genes, interrogation for sequence variants, insertion and deletion alterations, copy number variants, rearrangements, microsatellite instability, and tumor-mutation burden |
0474U | Hereditary pan-cancer (eg, hereditary sarcomas, hereditary endocrine tumors, hereditary neuroendocrine tumors, hereditary cutaneous melanoma), genomic sequence analysis panel of 88 genes with 20 duplications/deletions using next-generation sequencing (NGS), Sanger sequencing, blood or saliva, reported as positive or negative for germline variants, each gene |
0481U | IDH1 (isocitrate dehydrogenase 1 [NADP+]), IDH2 (isocitrate dehydrogenase 2 [NADP+]), and TERT (telomerase reverse transcriptase) promoter (eg, central nervous system [CNS] tumors), next-generation sequencing (single-nucleotide variants [SNV], deletions, and insertions (New 10/01/2024) |
0565U | Oncology (hepatocellular carcinoma), next-generation sequencing methylation pattern assay to detect 6626 epigenetic alterations, cell-free DNA, plasma, algorithm reported as cancer signal detected or not detected (New 07/01/2025) |
0571U | Oncology (solid tumor), DNA (80 genes) and RNA (10 genes), by next-generation sequencing, plasma, including single-nucleotide variants, insertions/deletions, copy-number alterations, microsatellite instability, and fusions, reported as clinically actionable variants (New 07/01/2025) |
81120 | IDH1 (isocitrate dehydrogenase 1 [NADP+], soluble) (eg, glioma), common variants (eg, R132H, R132C) |
81121 | IDH2 (isocitrate dehydrogenase 2 [NADP+], mitochondrial) (eg, glioma), common variants (eg, R140W, R172M) |
81432 | Hereditary breast cancer-related disorders (eg, hereditary breast cancer, hereditary ovarian cancer, hereditary endometrial cancer, hereditary pancreatic cancer, hereditary prostate cancer), genomic sequence analysis panel, 5 or more genes, interrogation for sequence variants and copy number variants; 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 (Revised 01/01/2025) |
81433 | Hereditary breast cancer-related disorder (eg, hereditary breast cancer, hereditary ovarian cancer, hereditary endometrial cancer); duplication/deletion analysis panel, must include analyses for BRCA1, BRCA2, MLH1, MSH2, and STK11 (Deleted 12/31/2024) |
81437 | Hereditary neuroendocrine tumor-related disorders (eg, medullary thyroid carcinoma, parathyroid carcinoma, malignant pheochromocytoma or paraganglioma), genomic sequence analysis panel, 5 or more genes, interrogation for sequence variants and copy number variants; genomic sequence analysis panel, must include sequencing of at least 6 genes, including MAX, SDHB, SDHC, SDHD, TMEM127, and VHL (Revised 01/01/2025) |
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 (Deleted 12/31/2024) |
81445 | Solid organ neoplasm, genomic sequence analysis panel, 5-50 genes, interrogation for sequence variants and copy number variants or rearrangements, if performed; DNA analysis or combined DNA and RNA analysis |
81450 | Hematolymphoid neoplasm or disorder, genomic sequence analysis panel, 5-50 genes, interrogation for sequence variants, and copy number variants or rearrangements, or isoform expression or mRNA expression levels, if performed; DNA analysis or combined DNA and RNA analysis |
814550 | Solid organ or hematolymphoid neoplasm or disorder, 51 or greater genes, genomic sequence analysis panel, interrogation for sequence variants and copy number variants or rearrangements, or isoform expression or mRNA expression levels, if performed; DNA analysis or combined DNA and RNA analysis |
81457 | Solid organ neoplasm, genomic sequence analysis panel, interrogation for sequence variants; DNA analysis, microsatellite instability |
81458 | Solid organ neoplasm, genomic sequence analysis panel, interrogation for sequence variants; DNA analysis, copy number variants and microsatellite instability |
81459 | Solid organ neoplasm, genomic sequence analysis panel, interrogation for sequence variants; DNA analysis or combined DNA and RNA analysis, copy number variants, microsatellite instability, tumor mutation burden, and rearrangements) |
81462 | Solid organ neoplasm, genomic sequence analysis panel, cell-free nucleic acid (eg, plasma), interrogation for sequence variants; DNA analysis or combined DNA and RNA analysis, copy number variants and rearrangements |
81463 | Solid organ neoplasm, genomic sequence analysis panel, cell-free nucleic acid (eg, plasma), interrogation for sequence variants; DNA analysis, copy number variants, and microsatellite instability |
81464 | Solid organ neoplasm, genomic sequence analysis panel, cell-free nucleic acid (eg, plasma), interrogation for sequence variants; DNA analysis or combined DNA and RNA analysis, copy number variants, microsatellite instability, tumor mutation burden, and rearrangements |
81479 | Unlisted molecular pathology procedure |
HCPCS | |
ICD-10 Procedure | |
ICD-10 Diagnosis |
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