Summary & Overview
CPT 0158U: MLH1 mRNA Sequence Analysis (CustomNext® + RNA)
CPT code 0158U is a Proprietary Laboratory Analyses (PLA) code for the CustomNext® + RNA: MLH1 test from Ambry Genetics®, used for mRNA sequence analysis of the MLH1 gene alongside the primary full-sequence analysis code. As a PLA code, 0158U identifies a single manufacturer- or lab-specific molecular diagnostic assay, making it important for lab reporting, claims processing, and manufacturer-specific coverage policies. Nationally, PLA codes like 0158U affect how payers and providers document test specificity and communicate clinical utility for hereditary cancer and genetic evaluation workflows.
Key payers discussed include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. Readers will find a concise overview of what the code represents, typical service settings, and the payer landscape relevant to this PLA molecular test. The publication also outlines benchmark considerations, policy and coverage update alerts, coding relationships with the primary full sequence analysis, and clinical context for MLH1 mRNA analysis in hereditary cancer evaluation. Data not available in the input is noted where applicable; the summary focuses on nationally relevant implications for billing, documentation, and payer engagement for this lab-specific molecular diagnostic code.
Billing Code Overview
CPT code 0158U is a Proprietary Laboratory Analyses (PLA) code that applies specifically to the CustomNext® + RNA: MLH1 test from Ambry Genetics®. The code is reported for mRNA sequence analysis of the MLH1 gene when performed in conjunction with the primary code for full sequence analysis. This PLA designation means the code represents a unique, manufacturer- or lab-specific molecular diagnostic assay.
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Service type: Laboratory molecular diagnostic testing for MLH1 mRNA sequence analysis
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Typical site of service: Clinical laboratory or reference laboratory setting
Clinical & Coding Specifications
Clinical Context
A patient with a personal or family history suggestive of Lynch syndrome (hereditary nonpolyposis colorectal cancer) is referred for germline evaluation. The referring clinician — often a medical geneticist, genetic counselor, oncologist, or colorectal surgeon — orders comprehensive DNA sequence analysis of mismatch repair genes and, when indicated by prior testing or suspected splicing variants, reflex or concurrent RNA-based analysis of MLH1 to clarify variant effect on mRNA splicing. Sample collection is via peripheral blood draw or clinically accepted specimen for Ambry Genetics®. The laboratory performs mRNA sequence analysis using the CustomNext® + RNA: MLH1 assay (0158U) in conjunction with the primary CPT code for full sequence analysis to characterize splice-altering variants or to resolve variants of uncertain significance. Results return to the ordering provider and genetic counselor for integration into diagnosis, cascade testing recommendations, and management planning. Typical site of service is an outpatient clinic, specialty genetics center, or a certified diagnostic laboratory performing proprietary testing.
Coding Specifications
| Modifier | Description | When to Use |
|---|---|---|
26 | Professional component | Use when reporting only the professional (interpretation) portion of the test if the laboratory separates technical and professional components and billing requires it. |
52 | Reduced services | Use when the test is partially reduced or a limited portion of the assay is performed. |
53 | Discontinued procedure | Use if specimen processing or testing is started but discontinued for documented clinical reasons. |
62 | Two surgeons | Use when two surgeons of different specialties are required for related procedures; rarely applicable but included when coordinating surgical sample acquisition in the same operative encounter. |
78 | Return to operating room for related procedure following initial procedure | Use if surgical re-intervention related to specimen acquisition is performed; included for completeness. |
80 | Assistant surgeon | Use when an assistant surgeon is billing for an operative procedure associated with specimen collection. |
82 | Assistant surgeon (when qualified assistant unavailable) | Use when a qualified assistant surgeon is not available and an assistant is used for specimen procurement in a facility setting. |
AD | Advanced diagnostic laboratory tests (PLA) | Use to indicate a proprietary laboratory assay when payer requires explicit PLA modifier reporting. |
QX | Rendering provider is CLIA-certified independent laboratory | Use when the performing laboratory is an independent CLIA-certified lab rendering the test. |
QY | Ordering physician has financial relationship with lab under certain programs | Use where applicable per payer policy to indicate physician ordering relationship. |
FY | Pathology or laboratory services — technical component only | Use to indicate technical component billing when professional interpretation is billed separately. |
TC | Technical component | Use when reporting only the technical component of the test (laboratory processing, sequencing). |
SH | Diagnostic test performed in hospital outpatient setting | Use when the test is performed and billed in a hospital outpatient environment. |
SJ | Diagnostic test performed in independent laboratory setting | Use when the test is performed and billed in an independent laboratory. |
| Taxonomy Code | Specialty | Notes |
|---|---|---|
| 207Q00000X | Medical Genetics & Genomics | Ordering and interpreting clinicians for germline testing. |
| 2086S0102X | Medical Oncology | Oncologists ordering hereditary cancer panels and interpreting results for cancer management. |
| 207L00000X | Laboratory Genetics & Genomics | Laboratory specialists responsible for performing and validating the assay. |
| 2080P0206X | Colorectal Surgery | Surgeons who may order testing in coordination with surgical care for colorectal cancer patients. |
| 363LP0801X | Genetic Counseling | Genetic counselors who coordinate testing and communicate results to patients. |
Related Diagnoses
| ICD-10 Code | Description | Clinical Relevance |
|---|---|---|
Z15.09 | Genetic susceptibility to other malignant neoplasm | Used when a patient has known or suspected hereditary cancer predisposition prompting MLH1 RNA analysis. |
Z80.0 | Family history of malignant neoplasm of digestive organs | Family history indicating increased risk for colorectal cancer and relevance for MLH1 testing. |
Z84.81 | Family history of carrier of genetic disease | Documenting family genetic risk that supports germline testing including MLH1. |
C18.9 | Malignant neoplasm of colon, unspecified | Personal history of colorectal cancer where MLH1 testing may inform hereditary etiology. |
D44.5 | Neoplasm of uncertain or unknown behavior of colon | Used when tumor behavior uncertain and germline testing is part of evaluation. |
Related CPT Codes
| CPT Code | Description | Relationship to This Procedure |
|---|---|---|
81211 | BRCA1 gene analysis; full sequence analysis | Genetic panel or single-gene sequencing commonly performed alongside hereditary cancer evaluation; not MLH1-specific but often ordered in parallel for comprehensive risk assessment. |
81216 | MLH1 (mismatch repair gene) full gene sequence analysis | Primary DNA sequence analysis of the MLH1 gene; 0158U is reported in conjunction with the primary code for full sequence analysis to capture RNA-based splice assessment. |
81479 | Unlisted molecular pathology procedure | Used when a specific proprietary PLA code is not available; historically used for specialized molecular tests. |
85379 | Molecular pathology multiple variant analysis (example) | Ancillary molecular pathology services that may be billed in workflows involving complex genetic testing; supports interpretation and variant confirmation. |
88360 | Morphometric analysis | Ancillary pathology procedures (e.g., tumor testing for mismatch repair protein expression by IHC) that may precede or complement germline RNA analysis. |