Concurrent DNA and RNA Genetic Testing Form

. Concurrent (paired) deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) genetic testing (also referred to as expanded RNA analysis) is a laboratory method that analyzes DNA in combination with RNA to purportedly aid with the detection, diagnosis and management of cancer as well as classification of variants of unknown significance (VUS). Paired testing may be offered to an individual who is at increased risk for hereditary cancer and is performed after a negative or inconclusive DNA test result to identify additional variants (mutations). +RNAinsight is an example of paired genetic testing and is conducted as an add-on test for multigene hereditary cancer panels. For information regarding genetic testing for inherited cancer susceptibility, please refer to the following Medical Coverage Policies:

Concurrent DNA and RNA Genetic Testing Effective Date: 08/24/2023 Revision Date: 08/24/2023 Review Date: 08/24/2023 Policy Number: HUM-0604-002 Page: 2 of 6 Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing. Indication Susceptibility to breast, ovarian and pancreatic cancer Susceptibility to gastric cancer, melanoma- pancreatic cancer syndrome, multiple endocrine neoplasia, paraganglioma/ pheochromocytoma, retinoblastoma and von Hippel-Lindau syndrome Susceptibility to colorectal cancer Related Medical Coverage Policy Genetic Testing for Breast, Ovarian and Pancreatic Cancer Susceptibility Genetic Testing for Cancer Susceptibility Genetic Testing for Colorectal Cancer Susceptibility For information regarding genetic testing for the following, please refer to Genetic Testing Medical Coverage Policy: • DNA banking or preservation • General population screening
• Individual 17 years of age or younger for adult-onset conditions • Interpretation and reporting for molecular pathology procedure • Polygenic risk score (PRS) and single nucleotide polymorphisms (SNPs)
• Repeat germline or somatic genetic testing • Retrieved archival tissue Humana recognizes that the field of genetic testing is rapidly changing and that other tests may become available. Coverage Determination Any state mandates for paired DNA and RNA genetic testing take precedence over this medical coverage policy.
Genetic testing may be excluded by certificate. Please consult the member’s individual certificate regarding Plan coverage. Humana members may NOT be eligible under the Plan for concurrent DNA and RNA genetic testing including, but may not be limited to: • +RNAinsight for ATM mRNA sequence analysis (0136U) See the DISCLAIMER. All Humana member health plan contracts are NOT the same. All legislation/regulations on this subject may not be included. This document is for informational purposes only.

Concurrent DNA and RNA Genetic Testing Effective Date: 08/24/2023 Revision Date: 08/24/2023 Review Date: 08/24/2023 Policy Number: HUM-0604-002 Page: 3 of 6 Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing. • +RNAinsight for BRCA1/2 mRNA sequence analysis (0138U) • +RNAinsight for BreastNext hereditary breast cancer-related disorders targeted mRNA sequence analysis (0131U) • +RNAinsight for CancerNext hereditary pan cancer targeted mRNA sequence analysis (0134U) • +RNAinsight for ColoNext hereditary colon cancer disorders targeted mRNA sequence analysis panel (0130U) • +RNAinsight for GYNPlus hereditary gynecological cancer targeted mRNA sequence analysis (0135U) • +RNAinsight for OvaNext hereditary ovarian cancer-related disorders targeted mRNA sequence analysis (0132U) • +RNAinsight for PALB2 mRNA sequence analysis (0137U) • +RNAinsight for ProstateNext hereditary prostate cancer-related disorders targeted mRNA sequence analysis (0133U) These are considered experimental/investigational as they are not identified as widely used and generally accepted for the proposed uses as reported in nationally recognized peer-reviewed medical literature published in the English language. Background Additional information about cancer may be found from the following websites: • American Cancer Society • National Cancer Institute • National Library of Medicine Medical Alternatives Physician consultation is advised to make an informed decision based on an individual’s health needs.
See the DISCLAIMER. All Humana member health plan contracts are NOT the same. All legislation/regulations on this subject may not be included. This document is for informational purposes only.

Concurrent DNA and RNA Genetic Testing Effective Date: 08/24/2023 Revision Date: 08/24/2023 Review Date: 08/24/2023 Policy Number: HUM-0604-002 Page: 4 of 6 Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing. Humana may offer a disease management program for this condition. The member may call the number on his/her identification card to ask about our programs to help manage his/her care. Provider Claims Codes Any CPT, HCPCS or ICD codes listed on this medical coverage policy are for informational purposes only. Do not rely on the accuracy and inclusion of specific codes. Inclusion of a code does not guarantee coverage and or reimbursement for a service or procedure. CPT® Code(s) 0130U 0131U 0132U 0133U 0134U Description Comments 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
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) 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) Hereditary prostate cancer-related disorders, targeted mRNA sequence analysis panel (11 genes) (List separately in addition to code for primary procedure) 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) Not Covered Not Covered Not Covered Not Covered Not Covered See the DISCLAIMER. All Humana member health plan contracts are NOT the same. All legislation/regulations on this subject may not be included. This document is for informational purposes only.

Concurrent DNA and RNA Genetic Testing Effective Date: 08/24/2023 Revision Date: 08/24/2023 Review Date: 08/24/2023 Policy Number: HUM-0604-002 Page: 5 of 6 Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing. 0135U 0136U 0137U 0138U 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) ATM (ataxia telangiectasia mutated) (eg, ataxia telangiectasia) mRNA sequence analysis (List separately in addition to code for primary procedure) PALB2 (partner and localizer of BRCA2) (eg, breast and pancreatic cancer) mRNA sequence analysis (List separately in addition to code for primary procedure) 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) Not Covered Not Covered Not Covered Not Covered CPT® Category III Code(s) No code(s) identified HCPCS Code(s) No code(s) identified References

3. Description Comments Description Comments Karam R, Conner B, LaDuca H, et al. Assessment of diagnostic outcomes of RNA genetic testing for hereditary cancer. JAMA Netw Open. 2019; 2(10):e1913900. https://www.ncbi.nlm.nih.gov/pmc. Accessed October 11,

   2021. Landrith T, Li B, Cass AA, et al. Splicing profile by capture RNA-seq identifies pathogenic germline variants in tumor suppressor genes. NPJ Precis Oncol. 2020;4:4. https://www.ncbi.nlm.nih.gov/pmc. Accessed October 11, 2021. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Genetic/familial high-risk assessment: breast, ovarian See the DISCLAIMER. All Humana member health plan contracts are NOT the same. All legislation/regulations on this subject may not be included. This document is for informational purposes only.

   Concurrent DNA and RNA Genetic Testing Effective Date: 08/24/2023 Revision Date: 08/24/2023 Review Date: 08/24/2023 Policy Number: HUM-0604-002 Page: 6 of 6 Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing. and pancreatic. https://www.nccn.org. Updated February 13, 2023. Accessed July 28, 2023.
   See the DISCLAIMER. All Humana member health plan contracts are NOT the same. All legislation/regulations on this subject may not be included. This document is for informational purposes only.