CPT 81325 PMP22 Sequencing Reimbursement

CPT code 81325 represents full-gene sequencing of the peripheral myelin protein 22 (PMP22) gene, a molecular diagnostic test used to detect sequence variants that can cause inherited peripheral neuropathies. Nationally, this code captures a specialized laboratory service relevant for neuromuscular and genetic diagnostic workflows and influences coverage determinations, laboratory billing practices, and utilization monitoring for rare genetic conditions. Key payers covered in this analysis include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. Readers will find a concise overview of the code's clinical context, typical sites of service, and the kinds of documentation and service lines associated with molecular genetic testing. The publication summarizes payer coverage patterns and common modifier usage where available, highlights benchmark considerations for laboratory billing, and outlines the clinical scenarios that commonly drive use of full-gene PMP22 sequencing. Data gaps are noted as "Data not available in the input." The content is aimed at billing managers, laboratory directors, and policy analysts seeking a national perspective on coding and reimbursement implications for comprehensive PMP22 sequencing.

Billing Code Overview

CPT code 81325 describes a laboratory procedure in which the technical component performs sequencing of the entire gene sequence for the peripheral myelin protein 22 (PMP22) gene. This service involves laboratory analysis of DNA to identify sequence variants across the full coding region of the PMP22 gene.

Service type: Clinical molecular diagnostic laboratory testing (full-gene sequencing)
Typical site of service: Clinical laboratory or reference molecular diagnostics laboratory

Clinical Context

A 28-year-old patient presents to a neuromuscular clinic with progressive distal limb weakness, foot deformities (pes cavus), sensory loss, and a family history of hereditary neuropathy. The neurologist documents concern for Charcot-Marie-Tooth disease or another hereditary demyelinating neuropathy and orders comprehensive genetic testing of the peripheral myelin protein 22 gene. A blood sample is collected in the outpatient phlebotomy lab and sent to a molecular diagnostics laboratory. The molecular lab analyst performs the technical sequencing assay to analyze the entire coding sequence and relevant intronic regions of the PMP22 gene, interprets sequence quality metrics, and generates a technical report. The laboratory issues the technical component of the genetic test; a separate interpretation report and clinical correlation are provided by the ordering clinician or a board-certified molecular geneticist when applicable. Typical sites of service are outpatient ambulatory clinics, independent diagnostic laboratories, hospital-based molecular diagnostics laboratories, and specialized genetics centers. Billing uses the technical component; modifier use depends on professional/technical split, multiple procedures, or special circumstances such as unusual complexity or specimen issues.

Coding Specifications

Modifier	Description	When to Use
`26`	Professional component	When reporting only the interpretation/reporting done by a physician or qualified geneticist separate from the laboratory technical sequencing.

Taxonomy Code	Specialty	Notes
2085N0006X	Molecular Diagnostic Genetics	Laboratory specialists who perform molecular sequencing and technical analysis.
2080P0206X	Clinical Pathology	Pathologists overseeing molecular diagnostic laboratories and quality control.
207Q00000X	Medical Genetics	Medical geneticists who provide clinical interpretation and correlation (professional component).
363L00000X	Genetic Counselor	Genetic counselors involved in pre- and post-test counseling and result communication.
207L00000X	Neurology	Neurologists who order testing for hereditary neuropathies and integrate results into care.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`G60.0`	Hereditary motor and sensory neuropathy	Primary category for Charcot-Marie-Tooth disease and other hereditary demyelinating neuropathies where `PMP22` sequencing is indicated.
`G60.2`	Hereditary motor and sensory neuropathy, axonal	Relevant when assessing hereditary neuropathies with axonal features; sequencing may help subtype disease.
`G60.8`	Other hereditary and idiopathic neuropathies	Used for hereditary neuropathies not otherwise specified where `PMP22` testing may be considered.
`R20.2`	Paresthesia of skin	Symptom code frequently present in patients evaluated with `PMP22` genetic testing.
`M21.3`	Hammer toe (acquired)	Represents foot deformities such as hammer toes or pes cavus that prompt evaluation for hereditary neuropathy.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`81325`	Analysis of entire coding region and relevant intronic regions of the peripheral myelin protein 22 (`PMP22`) gene (technical component)	Primary code describing the laboratory technical sequencing performed on the `PMP22` gene.
`81479`	Unlisted molecular pathology procedure	May be used for assays or add-on technical steps not represented by a specific CPT if needed for novel or atypical PMP22 analyses.
`88271`	FISH study for single target, probe set	Used when fluorescence in situ hybridization is performed to detect `PMP22` gene duplications or deletions as an alternate method to sequence analysis.
`81229`	Analysis of duplication and/or deletion (gene-level) — note: specific code for PMP22 duplication testing may vary	Used when targeted duplication/deletion testing (e.g., for PMP22 copy number changes) is performed instead of or in addition to sequence analysis.
`83891`	Molecular pathology procedure global (example code for interpretation)	Represents the professional interpretation/reporting component that may be billed separately from the technical component when performed by a physician or qualified laboratory director.

OpenPayer

Summary & Overview

CPT 81325: PMP22 Gene Full-Sequence Analysis