Summary & Overview

CPT 0138U: +RNAinsight™ mRNA Analysis for BRCA1/2

Headline: New PLA CPT code 0138U identifies Ambry Genetics’ +RNAinsight™ mRNA test to refine BRCA1/2 variant classification

Lead: CPT code 0138U designates a Proprietary Laboratory Analyses (PLA) test — the +RNAinsight™ for BRCA1/2 from Ambry Genetics — an mRNA sequencing assay used to improve classification of variants in the BRCA1 and BRCA2 genes associated with hereditary breast cancer. The code is reported in addition to the primary procedure.

What this represents and national importance: PLA CPT code 0138U captures a single-manufacturer, single-test molecular diagnostic that can influence clinical interpretation of BRCA1/2 variants. As variant reclassification affects genetic counseling, risk management, and downstream care decisions, having a distinct PLA code enables clearer tracking of utilization and potential policy decisions about coverage for specialized genomic assays.

Key payers covered: The analysis addresses commercial and public payers, including Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare.

What readers will learn: The publication provides benchmarks and utilization context for PLA-coded molecular diagnostics, outlines payer coverage landscapes and common modifier usage, and summarizes clinical context for mRNA-based variant classification in BRCA testing. It also highlights coding and billing considerations specific to PLA codes, and notes where input data is not available.

AetnaBlue Cross Blue ShieldCigna HealthUnitedHealthcareMedicare0138UCPTProprietary Laboratory AnalysesBRCA1BRCA2mRNA sequencinggenetic testingmolecular diagnosticsvariant classification

Billing Code Overview

CPT code 0138U is a Proprietary Laboratory Analyses (PLA) code for the +RNAinsight™ for BRCA1/2 test from Ambry Genetics. This service is an mRNA sequence analysis of the BRCA1 and BRCA2 genes designed to improve variant classification for genes implicated in hereditary breast cancer–related disorders. Report 0138U separately in addition to the code for the primary procedure.

Service Type: Proprietary laboratory mRNA sequence analysis for BRCA1/2 variant classification

Typical Site of Service: Clinical diagnostic laboratory or reference laboratory

Clinical & Coding Specifications

Clinical Context

A patient with a personal or family history suspicious for hereditary breast and ovarian cancer presents for genetic evaluation. Prior germline DNA testing of BRCA1/BRCA2 returned one or more variants of uncertain significance (VUS) or a likely pathogenic variant with unclear splicing consequences. The clinical team (genetic counselor and ordering physician — often a medical geneticist, oncologist, or breast surgeon) orders the Ambry Genetics +0138U +RNAinsight™ for BRCA1/2 test to perform mRNA sequence analysis from a blood or other appropriate tissue specimen. The lab receives a properly labeled specimen with the completed requisition and clinical indications such as family history of breast/ovarian cancer, early-onset breast cancer, or an identified BRCA variant requiring splicing assessment. The laboratory performs RNA extraction, reverse transcription, targeted amplification and sequencing of BRCA1 and BRCA2 transcripts, and bioinformatic interpretation to clarify the effect of DNA variants on RNA splicing and variant classification. Results are returned to the ordering provider and genetic counselor and are used to refine variant classification, inform risk assessment, cascade testing recommendations for relatives, and guide management decisions such as increased surveillance, risk-reducing surgery consideration, or targeted therapy eligibility when applicable. Typical site of service is an outpatient clinic or genetics center for specimen collection and a certified molecular diagnostic laboratory for test performance. Service type: Proprietary Laboratory Analysis (PLA) — specialized molecular diagnostic test reported in addition to the primary procedure.

Coding Specifications

Modifier	Description	When to Use

`26`	Professional component	Use when billing separately for the professional (interpretation) portion if the lab reports technical and professional components separately and payer requires split billing.
`TC`	Technical component	Use when billing only the technical portion (laboratory processing and sequencing) if split from professional component.
`59` not listed; alternative `76`/`77` not listed — adhere to provided modifiers only.	Data not available in the input.	Data not available in the input.
`22`	Increased procedural services	Use when the lab documents substantially greater effort or complexity in processing or interpretation beyond typical requirements (payer policies vary).
`52`	Reduced services	Use when testing is partially performed or limited, such as inadequate sample requiring partial assay.
`53`	Discontinued procedure	Use if testing is started but then discontinued for valid documented reasons (e.g., sample lost, degraded).
`62`	Two surgeons — co-surgery	Rarely applicable; included for completeness when multiple surgical providers are billing a primary procedure that generated the need for testing.
`80`	Assistant surgeon	Rarely applicable; use when an assistant surgeon is involved in a procedure associated with the specimen collection.
`AD`	Medical supervision by a teaching physician — primary service	Use when a teaching physician directly supervises specimen collection or ordering in a resident-teaching setting and payer requires the modifier.
`AS`	Physician assistant, nurse practitioner, or clinical nurse specialist services	Use when an advanced practice provider orders or collects the specimen per payer rules.
`QK`	Medical direction of two to four concurrent anesthesia procedures	Not typically applicable to lab testing; include only when relevant to an associated procedural anesthesia event.
`QX`	CRNA service with medical direction	Not typically applicable; use only if anesthesia services tied to specimen collection are billed.
`QY`	Medical direction of one CRNA by an anesthesiologist	As above, rarely applicable.
`SH`	Diagnostic radiology services — assistant surgeon	Rarely applicable; use only if a radiology assistant is involved in an associated imaging-guided biopsy that produced the specimen.

Taxonomy Code	Specialty	Notes
`207L00000X`	Medical Genetics	Most common ordering specialty; interprets and orders hereditary cancer RNA testing.
`208D00000X`	Oncology	Medical oncologists order testing for therapeutic implications and hereditary risk assessment.
`207RG0300X`	Genetic Counseling	Genetic counselors coordinate testing, consent, and family risk communication.
`207M00000X`	Internal Medicine	Primary care or breast specialists may order testing in coordination with genetics.
`261QU0200X`	Surgical Oncology / Breast Surgery	Breast surgeons may order testing when surgical decisions hinge on variant classification.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`Z15.01`	Genetic susceptibility to malignant neoplasm of breast	Relevant for patients with family history or known BRCA variants undergoing RNA testing to clarify variant pathogenicity.
`Z15.09`	Genetic susceptibility to other malignant neoplasm (includes ovarian susceptibility)	Used when assessing hereditary risk for ovarian cancer associated with BRCA variants.
`C50.9`	Malignant neoplasm of breast, unspecified	Used when a patient with breast cancer undergoes genetic workup including RNA splicing analysis for therapeutic or familial implications.
`D44.6`	Neoplasm of uncertain behavior of breast	Relevant when histology is uncertain and genetic variant interpretation may impact classification and management.
`Z80.3`	Family history of malignant neoplasm of breast	Common indication for genetic testing and variant clarification using RNA analysis.
`Z80.41`	Family history of malignant neoplasm of ovary	Indicates family ovarian cancer history prompting BRCA RNA testing.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`0138U`	`+RNAinsight™ for BRCA1/2` mRNA sequence analysis to improve variant classification (Proprietary Laboratory Analysis)	Primary PLA code describing the specific mRNA assay performed by Ambry Genetics; reported in addition to primary procedure codes when applicable.
`81162`	Targeted genomic sequence analysis panel, somatic mutation, single gene (e.g., BRCA1, BRCA2), sequence analysis	May be billed when DNA-based targeted sequencing of BRCA1/2 is performed as the primary germline or somatic test prior to or alongside RNA analysis for variant identification.
`81161`	BRCA1 and BRCA2 full gene sequence analysis (if used - example)	DNA-based BRCA sequencing codes are commonly part of the workflow that identifies variants needing RNA follow-up; billing depends on assay and payer policy.
`88360`	Immunohistochemistry or special staining interpretation	May be associated when tissue-based assays or ancillary studies are performed on surgical specimens that also undergo molecular testing; relevance depends on specimen type.
`80502`	Pharmacogenomic analysis (example)	Occasionally related when molecular profiling informs therapeutic decisions in oncology; include only when clinically performed in the same episode of care.