Billing and Coding: MolDX: Targeted and Comprehensive Genomic Profile Next-
Generation Sequencing Testing in Cancer

  **Next Generation Sequencing (NGS)**

NGS allows identification of somatic and/or germline alterations in multiple
genes simultaneously. This guideline focuses on Targeted and Comprehensive
Genomic Profile testing for somatic variant detection using tumor tissue only-
based panels for cancer.

 Definitions:

**Targeted Tumor Panels**

Targeted Next-Generation Sequencing (NGS) panels are hereby defined as tests
that identify somatic alterations known to occur in certain regions (i.e.,
**'hotspots'** ) within specific genes of interest for cancer management
(i.e., diagnosis, selection of molecularly targeted therapies, prognosis in a
context where prognostic classification is essential for treatment selection).
Generally, these NGS panels can detect single nucleotide variants (SNVs) and
small insertions or deletions (INDELs) within these regions. These alterations
typically represent response or lack of response to corresponding targeted
cancer therapies. The hotspot test should include relevant regions in the
genes required for companion diagnostic testing and/or known to be necessary
for proper patient management.

**Comprehensive Genomic Profile (CGP) Testing**

CGP refers to NGS-based molecular assays that provide additional insight
beyond individual gene hotspots; these assays seek to describe the genomic
makeup of a tumor and can help identify underlying mechanisms of disease to
guide clinical decision making. These tests include not only mutations in
individual relevant genes, but also patterns of mutations across related genes
in established cancer pathways and often include an assessment of overall
mutational burden. These tests typically involve sequencing of entire exonic
regions of genes of interest (within a comprehensive gene panel or whole exome
sequencing), and may also include selected intronic regions. CGP can detect
multiple types of molecular alterations (i.e., SNVs, small and large INDELs,
copy number alterations (CNAs), structural variants (SVs), and splice-site
variants) in a single assay. Patterns of mutations seen across multiple genes
may be used to infer clinically relevant etiologies, such as DNA mismatch
repair deficiency and microsatellite instability, and total mutational
load/burden (TMB) may be determined. CGP testing may also include RNA
sequencing to detect structural variations, such as translocations or large
deletions, and to detect functional splicing mutations. CGP is not defined as
a targeted panel by MolDX.

  **CPT coding Instructions:**

**Targeted Panels**

To bill for targeted NGS gene panel services for somatic variant detection,
review CPT codes 81445 and 81450. The units of service (UOS) for an NGS gene
panel is one (UOS=1). Providers must also provide the approved DEX Z-Code
identifier for the test.

Effective July 1, 2017, laboratories with 2 to 4 genes on their targeted NGS
panel should use CPT 81479 and one (1) UOS along with their test identifier
(DEX Z-CodeTM) to represent this service on their claims.

**CGP**

As CGP testing is not defined as a targeted panel by MolDX, and it is a test
not currently satisfactorily described by any existing CPT code. Therefore, to
report a CGP service, test providers should use CPT code 81479 at this time,
in addition to the approved DEX Z-CodeTM for the test. Coverage of CGP is
limited to one test per surgical specimen, and precludes the use of any other
molecular testing on that specimen.

For NGS-based tests that do not fit under the above definitions of "targeted"
or "Comprehensive" panels, billing with the "Not Otherwise Classified" (NOC)
code 81479 along with the approved DEX Z-CodeTM identifier is appropriate.

Tier 1 and/or Tier 2 individual biomarker CPT codes should not be used for a
single gene or any combination of genes when testing is performed as part of a
NGS or other multiplexing technology panel.

Refer to [Billing and Coding: MolDX: Next-Generation Sequencing for Solid
Tumors A57831 ](https://www.cms.gov/medicare-coverage-
database/view/article.aspx?articleid=57831&ver=8&bc=0)for CPT/HCPCS codes and
ICD-10 codes relevant for solid tumors.

Refer to [Billing and Coding: MolDX: Next-Generation Sequencing Lab-Developed
Tests for Myeloid Malignancies and Suspected Myeloid Malignancies A57837
](https://www.cms.gov/medicare-coverage-
database/view/article.aspx?articleid=57837&ver=9&bc=0)for CPT/HCPCS codes and
ICD-10 codes relevant for myeloid malignancies.