CPT 0621U: TruD MDS Lyme Disease DNA Methylation Assay

CPT code 0621U is a Proprietary Laboratory Analyses (PLA) CPT code for the TruD MDS Lyme Disease test from TruDiagnostic™ Inc., a blood-based infectious disease assay that analyzes DNA methylation at more than 10,000 sites and uses an algorithm to report a positive or negative risk for Lyme borreliosis; service type: molecular diagnostic infectious disease testing, typical site of service: clinical laboratory or reference lab using whole blood samples.

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CPT 0621U: TruD MDS Lyme Disease DNA Methylation Assay

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Clinical & Coding Specifications

Clinical Context

A typical patient scenario involves an adult or pediatric patient presenting with signs or history suspicious for Lyme borreliosis (for example, tick exposure, erythema migrans, migratory arthralgia, cranial nerve palsy, or persistent non-specific symptoms after prior treatment). A clinician in an outpatient specialty setting (infectious disease clinic, primary care, or a genomic testing referral center) orders the TruD MDS Lyme Disease test (0621U) when there is diagnostic uncertainty after standard serologic testing or when a provider seeks additional molecular-level risk stratification.

Workflow: the clinician documents the clinical indication, obtains a whole blood sample per the laboratory’s specimen collection instructions, and sends the specimen to TruDiagnostic™ Inc. The laboratory performs DNA methylation analysis at >10,000 CpG sites, applies its proprietary algorithm, and returns a report indicating a positive or negative risk for Lyme borreliosis. Results are reviewed by the ordering clinician, correlated with clinical findings, and used to support diagnostic decision-making and management planning.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`36415`	Collection of venous blood by venipuncture	Typical specimen collection method for whole blood sent for the test.
`81025`	Urine pregnancy test, by visual color comparison methods (single test)	Performed prior to some treatments (e.g., before antibiotics that are teratogenic) in women of childbearing potential when clinically indicated; may be part of workflow though not required by the test itself.
`80053`	Comprehensive metabolic panel	Common accompanying laboratory tests to evaluate baseline organ function prior to treatment decisions influenced by diagnostic results.
`86328`	Antibody; Lyme disease (Borrelia spp.), multiplex or specific serologic assays	Standard serologic testing often performed before or alongside advanced molecular/epigenetic testing for Lyme disease.
`81479`	Unlisted molecular pathology procedure	Occasionally used for reporting molecular tests when no specific PLA or CPT exists, though `0621U` is the specific PLA for TruD MDS Lyme and should be used when applicable.

Related Modifiers

6 rows

Modifier	Description	When to Use
26	Modifier 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…
59	Modifier 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…
24	Modifier 24 denotes an unrelated evaluation and management (E/M) service performed by the same physician or qualified healthcare professional during a postoperative global period. Per CPT guidance,…	- Use modifier 24 when you report an evaluation and management (E/M) service performed by the same physician or same-specialty group during a procedure’s postoperative global period that is unrelated…
25	CPT modifier 25 indicates that on the same day as another procedure or service, the same physician or other qualified health care professional provided a significant, separately identifiable…	- When to apply: Use modifier 25 only on an E/M code to indicate the same provider delivered a significant, separately identifiable E/M service on the same day as another procedure or service — i.e.,…
90	Modifier ‑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…
91	Modifier 91 — “Repeat Clinical Diagnostic Laboratory Test” — is appended when the exact same CPT laboratory test is performed more than once for the same patient on the same day because serial,…	- Use modifier 91 when the exact same CPT laboratory test is performed more than once on the same patient on the same date because serial or repeated testing is medically necessary to monitor…

Related Provider Taxonomies

8 rows

Taxonomy Code	Specialty	Notes
207Q00000X	Family Medicine Physician	Family Medicine is the medical specialty which is concerned with the total health care of the individual and the family. It is the specialty in breadt…
207L00000X	Anesthesiology Physician	An anesthesiologist is trained to provide pain relief and maintenance, or restoration, of a stable condition during and immediately following an opera…
207RC0000X	Cardiovascular Disease Physician	An internist who specializes in diseases of the heart and blood vessels and manages complex cardiac conditions such as heart attacks and life-threaten…
208D00000X	General Practice Physician	A physician who specializes in the general practice of diagnosing, treating, and managing patients with a variety of illnesses and conditions.
207K00000X	Allergy & Immunology Physician	An allergist-immunologist is trained in evaluation, physical and laboratory diagnosis, and management of disorders involving the immune system. Select…
2084S0012X	Sleep Medicine (Psychiatry & Neurology) Physician	A Psychiatrist or Neurologist who practices Sleep Medicine is certified in the subspecialty of sleep medicine and specializes in the clinical assessme…
1710I1003X	Independent Duty Medical Technicians	An Independent Duty Medical Technician (IDMT) is specially trained and educated to perform primary medical care, minor surgical services, and treatmen…
2080I0007X	Pediatric Clinical & Laboratory Immunology Physician	A pediatrician who specializes in clinical and laboratory immunology disease management.

Related Payer Policy Updates

Specialty: Genetic & Molecular Testing1 / 3

10 rows

Policy	Payer	Effective Date
RTM Testing of Homocysteine Metabolism-Related Conditions	Oscar Health	2026-10-01
Multimarker Serum Testing Related to Ovarian Cancer	Blue Cross Blue Shield - Rhode Island	2026-09-01
Genomic Profiling for Selecting Targeted Cancer Therapies	Blue Cross Blue Shield - Rhode Island	2026-09-01
Whole Exome and Whole Genome Sequencing for Diagnosis of Genetic Disorders	Blue Cross Blue Shield - Rhode Island	2026-09-01
Biomarker and Genetic/Molecular Testing Coverage and Prior Authorization	Blue Cross Blue Shield - Rhode Island	2026-09-01
Non-Invasive Prenatal Testing (NIPT)	univerahealthcare	2026-08-17
Lumizyme (alglucosidase alfa) — Pompe Disease (acid alpha‑glucosidase deficiency)	Cigna	2026-08-15
Molecular Oncology Testing for Solid Tumor Cancer Diagnosis, Prognosis, and Treatment Decisions	Colorado Rocky Mountain Health Plans	2026-08-01
Molecular Oncology Testing for Hematologic Cancer Diagnosis, Prognosis, and Treatment Decisions	Colorado Rocky Mountain Health Plans	2026-08-01
Carrier Testing Panels for Genetic Diseases	Colorado Rocky Mountain Health Plans	2026-08-01

CPT 0001U: PreciseType HEA Erythrocyte Antigen Genotyping

CPT-0002U-POLYPDX-URINE-METABOLOMIC-ASSAY-ADENOMATOUS-POLYP-RISK

CPT 0002U: PolypDX™ Urine Metabolomic Risk Assay

CPT-0003U-OVAR-A-NEXT-GENERATION-OVARIAN-CANCER-RISK-ASSAY

CPT 0003U: Overa (MIA2G) Ovarian Cancer Risk Assay

CPT-0005U-PROSTATE-EXOSOMEDX-INTELLISCORE-GENE-EXPRESSION-URINE-TEST

CPT 0005U: ExosomeDx Prostate (IntelliScore) urine gene expression test

CPT-0007U-TOXPROTECT-URINE-DRUG-SCREEN-WITH-DNA-AUTHENTICATION

CPT 0007U: ToxProtect Urine Drug Screen With DNA Authentication

CPT-0008U-H-PYLORI-ANTIBIOTIC-RESISTANCE-SEQUENCING-PANEL

CPT 0008U: H. pylori Antibiotic Resistance Gene Panel

CPT-0009U-DEPARRAY-HER2-FISH-TUMOR-CELL-ISOLATION

CPT 0009U: DEPArray HER2 Tumor‑Cell Isolation with FISH Analysis

CPT-0010U-BACTERIAL-TYPING-WHOLE-GENOME-SEQUENCING-MAYO-CLINIC

CPT 0010U: Bacterial Typing by Whole Genome Sequencing, Mayo Clinic

CPT-0011U-CORDANT-CORE-ALGORITHMIC-ORAL-FLUID-DRUG-TEST

CPT 0011U: Oral Fluid Drug Test with Algorithmic Steady‑State Comparison

CPT-0016U-BCR-ABL1-MAJOR-MINOR-FUSION-TRANSCRIPT-TESTING

CPT 0016U: BCR–ABL1 Major and Minor Breakpoint Fusion Transcripts

Showing 1–10 of 536

Frequently Asked Questions

References

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.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.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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Clinical & Coding Specifications

Clinical Context

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`36415`	Collection of venous blood by venipuncture	Typical specimen collection method for whole blood sent for the test.
`81025`	Urine pregnancy test, by visual color comparison methods (single test)	Performed prior to some treatments (e.g., before antibiotics that are teratogenic) in women of childbearing potential when clinically indicated; may be part of workflow though not required by the test itself.
`80053`	Comprehensive metabolic panel	Common accompanying laboratory tests to evaluate baseline organ function prior to treatment decisions influenced by diagnostic results.
`86328`	Antibody; Lyme disease (Borrelia spp.), multiplex or specific serologic assays	Standard serologic testing often performed before or alongside advanced molecular/epigenetic testing for Lyme disease.
`81479`	Unlisted molecular pathology procedure	Occasionally used for reporting molecular tests when no specific PLA or CPT exists, though `0621U` is the specific PLA for TruD MDS Lyme and should be used when applicable.

Related Modifiers

6 rows

Modifier	Description	When to Use
26	Modifier 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…
59	Modifier 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…
24	Modifier 24 denotes an unrelated evaluation and management (E/M) service performed by the same physician or qualified healthcare professional during a postoperative global period. Per CPT guidance,…	- Use modifier 24 when you report an evaluation and management (E/M) service performed by the same physician or same-specialty group during a procedure’s postoperative global period that is unrelated…
25	CPT modifier 25 indicates that on the same day as another procedure or service, the same physician or other qualified health care professional provided a significant, separately identifiable…	- When to apply: Use modifier 25 only on an E/M code to indicate the same provider delivered a significant, separately identifiable E/M service on the same day as another procedure or service — i.e.,…
90	Modifier ‑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…
91	Modifier 91 — “Repeat Clinical Diagnostic Laboratory Test” — is appended when the exact same CPT laboratory test is performed more than once for the same patient on the same day because serial,…	- Use modifier 91 when the exact same CPT laboratory test is performed more than once on the same patient on the same date because serial or repeated testing is medically necessary to monitor…

Related Provider Taxonomies

8 rows

Taxonomy Code	Specialty	Notes
207Q00000X	Family Medicine Physician	Family Medicine is the medical specialty which is concerned with the total health care of the individual and the family. It is the specialty in breadt…
207L00000X	Anesthesiology Physician	An anesthesiologist is trained to provide pain relief and maintenance, or restoration, of a stable condition during and immediately following an opera…
207RC0000X	Cardiovascular Disease Physician	An internist who specializes in diseases of the heart and blood vessels and manages complex cardiac conditions such as heart attacks and life-threaten…
208D00000X	General Practice Physician	A physician who specializes in the general practice of diagnosing, treating, and managing patients with a variety of illnesses and conditions.
207K00000X	Allergy & Immunology Physician	An allergist-immunologist is trained in evaluation, physical and laboratory diagnosis, and management of disorders involving the immune system. Select…
2084S0012X	Sleep Medicine (Psychiatry & Neurology) Physician	A Psychiatrist or Neurologist who practices Sleep Medicine is certified in the subspecialty of sleep medicine and specializes in the clinical assessme…
1710I1003X	Independent Duty Medical Technicians	An Independent Duty Medical Technician (IDMT) is specially trained and educated to perform primary medical care, minor surgical services, and treatmen…
2080I0007X	Pediatric Clinical & Laboratory Immunology Physician	A pediatrician who specializes in clinical and laboratory immunology disease management.

Related Payer Policy Updates

Specialty: Genetic & Molecular Testing1 / 3

10 rows

Policy	Payer	Effective Date
RTM Testing of Homocysteine Metabolism-Related Conditions	Oscar Health	2026-10-01
Multimarker Serum Testing Related to Ovarian Cancer	Blue Cross Blue Shield - Rhode Island	2026-09-01
Genomic Profiling for Selecting Targeted Cancer Therapies	Blue Cross Blue Shield - Rhode Island	2026-09-01
Whole Exome and Whole Genome Sequencing for Diagnosis of Genetic Disorders	Blue Cross Blue Shield - Rhode Island	2026-09-01
Biomarker and Genetic/Molecular Testing Coverage and Prior Authorization	Blue Cross Blue Shield - Rhode Island	2026-09-01
Non-Invasive Prenatal Testing (NIPT)	univerahealthcare	2026-08-17
Lumizyme (alglucosidase alfa) — Pompe Disease (acid alpha‑glucosidase deficiency)	Cigna	2026-08-15
Molecular Oncology Testing for Solid Tumor Cancer Diagnosis, Prognosis, and Treatment Decisions	Colorado Rocky Mountain Health Plans	2026-08-01
Molecular Oncology Testing for Hematologic Cancer Diagnosis, Prognosis, and Treatment Decisions	Colorado Rocky Mountain Health Plans	2026-08-01
Carrier Testing Panels for Genetic Diseases	Colorado Rocky Mountain Health Plans	2026-08-01

CPT 0001U: PreciseType HEA Erythrocyte Antigen Genotyping

CPT-0002U-POLYPDX-URINE-METABOLOMIC-ASSAY-ADENOMATOUS-POLYP-RISK

CPT 0002U: PolypDX™ Urine Metabolomic Risk Assay

CPT-0003U-OVAR-A-NEXT-GENERATION-OVARIAN-CANCER-RISK-ASSAY

CPT 0003U: Overa (MIA2G) Ovarian Cancer Risk Assay

CPT-0005U-PROSTATE-EXOSOMEDX-INTELLISCORE-GENE-EXPRESSION-URINE-TEST

CPT 0005U: ExosomeDx Prostate (IntelliScore) urine gene expression test

CPT-0007U-TOXPROTECT-URINE-DRUG-SCREEN-WITH-DNA-AUTHENTICATION

CPT 0007U: ToxProtect Urine Drug Screen With DNA Authentication

CPT-0008U-H-PYLORI-ANTIBIOTIC-RESISTANCE-SEQUENCING-PANEL

CPT 0008U: H. pylori Antibiotic Resistance Gene Panel

CPT-0009U-DEPARRAY-HER2-FISH-TUMOR-CELL-ISOLATION

CPT 0009U: DEPArray HER2 Tumor‑Cell Isolation with FISH Analysis

CPT-0010U-BACTERIAL-TYPING-WHOLE-GENOME-SEQUENCING-MAYO-CLINIC

CPT 0010U: Bacterial Typing by Whole Genome Sequencing, Mayo Clinic

CPT-0011U-CORDANT-CORE-ALGORITHMIC-ORAL-FLUID-DRUG-TEST

CPT 0011U: Oral Fluid Drug Test with Algorithmic Steady‑State Comparison

CPT-0016U-BCR-ABL1-MAJOR-MINOR-FUSION-TRANSCRIPT-TESTING

CPT 0016U: BCR–ABL1 Major and Minor Breakpoint Fusion Transcripts

Showing 1–10 of 536

Frequently Asked Questions

References

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.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.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.

Published by

Trek Health powers OpenPayer with a leading commercial payer intelligence platform, seamlessly converting fragmented payer data into actionable insights for provider organizations.

OpenPayer

CPT 0621U: TruD MDS Lyme Disease DNA Methylation Assay

Sign up for cpt 0621U policy alerts

OpenPayer

CPT 0621U: TruD MDS Lyme Disease DNA Methylation Assay

Sign up for cpt 0621U policy alerts

Clinical & Coding Specifications

Clinical Context

Related CPT Codes

Related Modifiers

Related Provider Taxonomies

Related Payer Policy Updates

Related Codes

References

Clinical & Coding Specifications

Clinical Context

Related CPT Codes

Related Modifiers

Related Provider Taxonomies

Related Payer Policy Updates

Related Codes

References

CPT 0621U: TruD MDS Lyme Disease DNA Methylation Assay

Sign up for cpt 0621U policy alerts

CPT 0621U: TruD MDS Lyme Disease DNA Methylation Assay

Sign up for cpt 0621U policy alerts

Clinical & Coding Specifications

Clinical Context

Related CPT Codes

Related Modifiers

Related Provider Taxonomies

Related Payer Policy Updates

Related Codes

What does CPT code 0621U represent?

Who orders 0621U and in what clinical settings is it used?

What specimen and collection procedure are associated with billing 0621U?

Which billing modifiers may be used with 0621U?

Which payers are referenced and will 0621U always be covered?

References

Clinical & Coding Specifications

Clinical Context

Related CPT Codes

Related Modifiers

Related Provider Taxonomies

Related Payer Policy Updates

Related Codes

What does CPT code 0621U represent?

Who orders 0621U and in what clinical settings is it used?

What specimen and collection procedure are associated with billing 0621U?

Which billing modifiers may be used with 0621U?

Which payers are referenced and will 0621U always be covered?

References