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    v1.0.31
    OpenPayerBilling CodesGenetic Analysis ProceduresCPT cpt-81321-pten-full-gene-sequencing
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    CPT 81321: PTEN Gene Full Sequence Analysis

    CPT code 81321 describes laboratory technical services for comprehensive sequencing of the PTEN (phosphatase and tensin homolog) gene, performed to analyze the entire coding sequence and detect sequence-level variants; the service type is molecular pathology / genetic sequencing, and the typical site of service is a clinical molecular diagnostics laboratory where the lab analyst conducts the sequencing assay and generates the technical data output.

    For related coverage guidance, see recent payer policy updates: Minimal Residual Disease (MRD) Testing for Cancer, Biomarker Testing Mandate, Prenatal (Fetal) Diagnostic Testing.

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    Clinical & Coding Specifications

    Clinical Context

    A 34-year-old patient with a personal and family history of early-onset breast cancer is referred to a genetics clinic for hereditary cancer risk assessment. The clinician orders comprehensive sequencing of the PTEN gene to evaluate for PTEN hamartoma tumor syndrome (including Cowden syndrome) because the patient meets clinical criteria (multiple hamartomas, personal thyroid lesion, and macrocephaly) and there is concern for pathogenic germline variants that influence surveillance and management. A phlebotomy draw is performed in the outpatient laboratory; the specimen is sent to a molecular diagnostics laboratory. A molecular laboratory technologist performs DNA extraction, library preparation, sequencing, and bioinformatic analysis across the entire coding region and relevant intronic boundaries of the PTEN gene. The laboratory issues a report describing detected sequence variants, variant classification (pathogenic, likely pathogenic, VUS, likely benign, benign), and recommended follow-up testing if applicable. Billing for the technical component of full-gene sequencing is submitted using 81321 with the laboratory’s usual place of service code (typically outpatient laboratory or independent diagnostic testing facility). Typical providers involved include medical geneticists, genetic counselors, oncologists, endocrinologists, and laboratory molecular pathologists. Turnaround time for routine testing is often 2–4 weeks; urgent testing may use modifier QK/QX workflows when applicable for targeted rapid testing, though 81321 denotes full-gene analysis rather than targeted single-variant assays.

    Related CPT Codes

    CPT CodeDescriptionRelationship to This Procedure
    81432Hereditary breast cancer panel, e.g., sequencing of multiple genes (e.g., BRCA1/2 and others); may include PTEN as part of multi-gene panelsPerformed alongside or instead of single-gene PTEN sequencing when broader hereditary cancer panel testing is indicated
    81211BRCA1 gene analysis, full gene sequenceAlternative or complementary hereditary cancer gene testing ordered based on family history
    81479Unlisted molecular pathology procedureUsed for novel or custom tests not otherwise specified; not typically used when 81321 is appropriate
    81220APC (adenomatous polyposis coli) gene analysis, full gene sequenceOrdered in parallel when gastrointestinal polyposis syndromes are considered alongside PTEN-related hamartoma syndromes
    88235High complexity molecular cytogenetics (e.g., FISH)May be performed in addition to sequencing if structural variants or copy number changes are suspected and require orthogonal confirmation

    Related Modifiers

    6 rows

    ModifierDescriptionWhen to Use
    26Modifier 26 (Professional Component) identifies and bills only the professional portion of a split service — the physician’s interpretation, report, and medical judgment — when the technical…- Use CPT Modifier -26 when you are billing only the professional component (PC) of a split‑bill eligible service—i.e., you performed the physician interpretation, medical judgment and prepared a…
    90Modifier ‑90 (Reference/Outside Laboratory) indicates that a laboratory test was performed by an entity other than the treating or reporting provider. The American Medical Association defines…- Use CPT modifier -90 when a laboratory test is performed by an outside/reference laboratory (an entity other than the treating or reporting physician or qualified professional) and the claim needs…
    59Modifier 59 indicates a distinct procedural service when two procedures that are not normally billed together are clinically and procedurally separate. The CPT definition (as reiterated by CMS)…- Use modifier -59 to report a distinct procedural service when documentation supports that the procedure reported is not normally billed together with another service on the same day because of a…
    52Modifier ‑52 (Reduced Services) indicates that a service or procedure was partially reduced or omitted at the provider’s discretion, allowing reporting of the basic procedure number with a qualifier…- Use modifier -52 when a physician or qualified health professional electively reduces or omits part of a procedure or service (for example, performing fewer required views or omitting a portion of…
    53Modifier 53 (Discontinued Procedure) signals that a surgical or diagnostic service was begun by the physician but terminated because of extenuating circumstances that threatened the patient’s…- Use modifier -53 when a physician/qualified healthcare professional has started a surgical or diagnostic procedure (e.g., anesthesia administered, incision or scope insertion) and then discontinues…
    22Modifier –22 (Increased Procedural Services) is used when a reported procedure is substantially more extensive than normally required. The CPT Manual and CMS state it may be appended only when the…- When to use: Append modifier -22 to a procedural CPT code when the service performed is substantially more extensive than the usual service described by that code — i.e., the procedure required…

    Related Provider Taxonomies

    8 rows

    Taxonomy Code
    207RG0100X
    208M00000X
    207RC0000X
    208000000X
    207L00000X
    246ZI1000X
    261QP2000X
    213ER0200X

    Related Payer Policy Updates

    Specialty: Genetic & Molecular Testing1 / 3

    10 rows

    PolicyPayerEffective Date
    Minimal Residual Disease (MRD) Testing for Cancerregence2027-01-01
    Biomarker Testing MandateBlue Cross Blue Shield - Rhode Island2027-01-01
    Prenatal (Fetal) Diagnostic TestingBlue Cross Blue Shield - Rhode Island2027-01-01
    Oral Cancer Screening and TestingOscar Health2027-01-01
    RTM Testing for Alpha-1 Antitrypsin DeficiencyOscar Health2027-01-01
    Cytochrome P450 Genotype-Guided Treatment Strategy Corporate Medical Policybcbsvermont2027-01-01
    Polygenic Risk ScoreBlue Cross Blue Shield - Rhode Island2026-12-01
    Gene Expression Profiling for Cutaneous MelanomaBlue Cross Blue Shield - Rhode Island2026-12-01
    Genetic Testing for Macular Degenerationregence2026-11-01
    Pharmacogenetic Panel Testing (for Ohio Only)Colorado Rocky Mountain Health Plans2026-11-01

    Related Codes

    CPT-81105-HPA-1-PLATELET-ANTIGEN-1-GENOTYPING-ITGB3-CD61

    CPT 81105: HPA-1 (ITGB3/CD61) Genotyping, Technical Component

    CPT-81106-HPA-2-T145M-GENETIC-ALLELE-ANALYSIS

    CPT 81106: HPA-2 (T145M) Platelet Antigen Genotyping

    CPT-81107-HPA-3-GENETIC-ANALYSIS-TECHNICAL-COMPONENT

    CPT 81107: HPA‑3 (I843S) Platelet Antigen Genotyping

    CPT-81108-HPA-4-R143Q-GENOTYPING

    CPT 81108: HPA-4 (R143Q) Genotyping

    CPT-81109-HPA-5-K505E-GENETIC-ANALYSIS

    CPT 81109: HPA-5 (K505E) Genotyping Test

    CPT-81110-HPA-6-R489Q-GENOTYPING

    CPT 81110: HPA-6 (R489Q) Genotyping, Technical Component

    CPT-81111-HPA-9-V837M-ALLELE-ANALYSIS

    CPT 81111: HPA-9 (V837M) Genotyping, Technical Test

    CPT-81112-HPA-15-GENETIC-ANALYSIS-S682Y

    CPT 81112: HPA-15 (S682Y) Platelet Antigen Genotyping

    CPT-81120-IDH1-MOLECULAR-DIAGNOSTIC-TEST

    CPT 81120: IDH1 Mutation Detection, Technical Component

    CPT-81121-IDH2-MOLECULAR-DIAGNOSTIC-TEST

    CPT 81121: IDH2 Mutation Detection, Technical Component

    Showing 1–10 of 199

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    Frequently Asked Questions

    References

    1. 1.CPT® Codes and Descriptions. AAPC. Retrieved Aug 11, 2026.Maintains the CPT code set's official descriptions and guidelines, licensed from the American Medical Association, used as the definitional source for CPT codes on this page.
    2. 2.HCPCS Quarterly Update. Centers for Medicare & Medicaid Services (CMS). Retrieved Aug 11, 2026.CMS's quarterly release of HCPCS Level II codes and short/long descriptors, the source for HCPCS code definitions and update history.
    3. 3.ICD-10-CM Full Code List. Centers for Medicare & Medicaid Services (CMS). Retrieved Aug 11, 2026.CMS's complete ICD-10-CM diagnosis code list, used to cross-reference diagnosis codes associated with this procedure or service.
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