Summary & Overview

CPT 0159U: mRNA Sequence Analysis of MSH2 (CustomNext® + RNA)

CPT code 0159U is a Proprietary Laboratory Analyses (PLA) code that identifies the Ambry Genetics® CustomNext® + RNA: MSH2 assay for mRNA sequence analysis of the MSH2 gene, reported alongside the primary full-sequence analysis code. PLA codes like 0159U matter nationally because they designate single-manufacturer or single-lab tests that can affect coding specificity, payer coverage decisions, and claims processing for molecular diagnostics. This code is used in the context of genetic and hereditary cancer testing and influences clinical interpretation when RNA-based analysis supplements DNA sequencing.

Key payers covered in this analysis include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. Readers will find an overview of clinical context for RNA-based MSH2 testing, payer coverage considerations for a PLA-designated assay, and where this service is typically performed. The publication outlines benchmarking and policy implications relevant to proprietary laboratory codes, including how PLA status can shape coding practices, claim adjudication, and communication between laboratories and payers. Data not available in the input includes reimbursement rates, payer-specific coverage policies, associated taxonomies, ICD-10 diagnoses, and related codes.

AetnaBlue Cross Blue ShieldCigna HealthUnitedHealthcareMedicare0159UCPTPLAmRNA sequencingMSH2molecular diagnosticsgenetic testinglaboratoryAmbry Genetics

Billing Code Overview

CPT code 0159U is a Proprietary Laboratory Analyses (PLA) code for the CustomNext® + RNA: MSH2 test from Ambry Genetics®. The code applies specifically to mRNA sequence analysis of the MSH2 gene when reported in conjunction with the primary code for full sequence analysis. This PLA code identifies a single manufacturer-specific laboratory assay rather than a broadly available test.

Service type: Molecular diagnostic testing — mRNA sequence analysis of MSH2

Typical site of service: Independent clinical laboratory or reference molecular diagnostics laboratory

Clinical & Coding Specifications

Clinical Context

A 42-year-old patient with a personal and family history suspicious for Lynch syndrome is referred for hereditary cancer genetic testing. The ordering clinician (geneticist or oncologist) requests full germline sequence analysis of mismatch repair genes and adds targeted mRNA analysis for the MSH2 gene to evaluate for splice-altering variants or aberrant transcript production. A blood sample is collected at an outpatient phlebotomy site or in a clinic, sent to Ambry Genetics® for testing. The laboratory performs the primary full sequence DNA analysis (reported under the primary CPT for full sequence analysis) and the proprietary CustomNext® + RNA: MSH2 assay reported with PLA code 0159U to provide mRNA sequence analysis results that clarify variant pathogenicity. Results are reported to the ordering provider and integrated into clinical decision-making for risk assessment, surveillance, and management. Typical sites of service include outpatient clinics, ambulatory surgical centers for pre-test counseling, and centralized clinical laboratories where the test is performed.

Coding Specifications

Modifier	Description	When to Use
`26`	Professional component	When reporting only the professional interpretation component if separated by the lab or physician.
`TC`	Technical component	When reporting only the technical component if billed separately by the performing laboratory.
`59`	Distinct procedural service (Note: `59` not in provided list)	Data not available in the input.
`22`	Increased procedural services	When work or resources significantly exceed typical for the assay (rare for PLA tests).
`52`	Reduced services	When the test is partially performed or limited in scope.
`53`	Discontinued procedure	If testing cannot be completed for a clinical or specimen-related reason prior to completion.
`62`	Two surgeons	Not typically applicable to lab PLA codes; use only if two qualified practitioners share work.
`78`	Unplanned return to operating/procedure room	Not applicable to this laboratory test; included in list but rarely used.
`80`	Assistant at surgery	Not applicable to this laboratory test.
`QX`	Modifier for ordering/servicing practitioner requirements	When a modifier is required to attest to ordering/servicing practitioner qualifications per payer.
`QY`	Attestation of ordering physician certification	When an ordering physician meets payer-specific lab test ordering requirements.
`AD`	Advanced care team (clinical staff)	When the service was provided in part by an advanced practice provider, per payer rules.
`AS`	Physician assistant, nurse practitioner, or clinical nurse specialist services	When those practitioners furnish the interpretation or order the test per payer policy.

Taxonomy Code	Specialty	Notes
`208D00000X`	Clinical Molecular Genetics Laboratory	Laboratories performing molecular diagnostic testing, including PLA assays.
`208000000X`	Clinical Pathology	Pathologists overseeing genetic testing and result interpretation.
`2086S0201X`	Genetic Counselor	Professionals ordering, counseling, and coordinating hereditary cancer testing.
`207R00000X`	Oncology	Medical oncologists who order germline testing for treatment or risk assessment.
`207L00000X`	Medical Genetics	Clinical geneticists involved in ordering and interpreting hereditary cancer panels.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`Z15.09`	Genetic susceptibility to other malignant neoplasms	Used when there is known or suspected hereditary cancer predisposition such as Lynch syndrome prompting germline and RNA analysis of MSH2.
`Z80.0`	Family history of malignant neoplasm of digestive organs	Family history of colorectal cancer supports testing of mismatch repair genes including MSH2.
`Z80.3`	Family history of malignant neoplasm of breast and female genital organs	Family history that may overlap with hereditary cancer syndromes prompting expanded testing.
`C18.9`	Malignant neoplasm of colon, unspecified	A personal history of colorectal cancer may trigger tumor and germline testing including MSH2 RNA analysis.
`C54.9`	Malignant neoplasm of corpus uteri, unspecified	Endometrial cancer is associated with Lynch syndrome; MSH2 RNA testing can clarify variant effects.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`81211`	BRCA1 gene analysis; full sequence analysis	Often performed on patients being evaluated for hereditary cancer syndromes alongside MSH2 testing when indicated by family history.
`81479`	Unlisted molecular pathology procedure	Occasionally used for novel or unlisted molecular tests not covered by a PLA code; not used when `0159U` applies.
`81292`	Mismatch repair genes (MLH1, MSH2, MSH6, PMS2) full sequence analysis, each	The primary full sequence analysis code(s) for mismatch repair gene testing that would be billed in conjunction with `0159U` when full MSH2 sequencing is performed.
`88360`	Morphometric analysis; computer-assisted	May be used when correlating molecular findings with tumor testing such as IHC scoring in pathology workflows.
`89390`	Molecular pathology procedure; interpretation and report	Represents professional interpretation services that may accompany molecular testing reports when billed separately.