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Official Description

Molecular pathology procedure, Level 4 (eg, analysis of single exon by DNA sequence analysis, analysis of >10 amplicons using multiplex PCR in 2 or more independent reactions, mutation scanning or duplication/deletion variants of 2-5 exons)

ANG (angiogenin, ribonuclease, RNase A family, 5) (eg, amyotrophic lateral sclerosis), full gene sequence

ARX (aristaless related homeobox) (eg, X-linked lissencephaly with ambiguous genitalia, X-linked intellectual disability), duplication/deletion analysis

CEL (carboxyl ester lipase [bile salt-stimulated lipase]) (eg, maturity-onset diabetes of the young [MODY]), targeted sequence analysis of exon 11 (eg, c.1785delC, c.1686delT)

CTNNB1 (catenin [cadherin-associated protein], beta 1, 88kDa) (eg, desmoid tumors), targeted sequence analysis (eg, exon 3)

DAZ/SRY (deleted in azoospermia and sex determining region Y) (eg, male infertility), common deletions (eg, AZFa, AZFb, AZFc, AZFd)

DNMT3A (DNA [cytosine-5-]-methyltransferase 3 alpha) (eg, acute myeloid leukemia), targeted sequence analysis (eg, exon 23)

EPCAM (epithelial cell adhesion molecule) (eg, Lynch syndrome), duplication/deletion analysis

F8 (coagulation factor VIII) (eg, hemophilia A), inversion analysis, intron 1 and intron 22A

F12 (coagulation factor XII [Hageman factor]) (eg, angioedema, hereditary, type III; factor XII deficiency), targeted sequence analysis of exon 9

FGFR3 (fibroblast growth factor receptor 3) (eg, isolated craniosynostosis), targeted sequence analysis (eg, exon 7)

(For targeted sequence analysis of multiple FGFR3 exons, use 81404)

GJB1 (gap junction protein, beta 1) (eg, Charcot-Marie-Tooth X-linked), full gene sequence

GNAQ (guanine nucleotide-binding protein G[q] subunit alpha) (eg, uveal melanoma), common variants (eg, R183, Q209)

Human erythrocyte antigen gene analyses (eg, SLC14A1 [Kidd blood group], BCAM [Lutheran blood group], ICAM4 [Landsteiner-Wiener blood group], SLC4A1 [Diego blood group], AQP1 [Colton blood group], ERMAP [Scianna blood group], RHCE [Rh blood group, CcEe antigens], KEL [Kell blood group], DARC [Duffy blood group], GYPA, GYPB, GYPE [MNS blood group], ART4 [Dombrock blood group]) (eg, sickle-cell disease, thalassemia, hemolytic transfusion reactions, hemolytic disease of the fetus or newborn), common variants

HRAS (v-Ha-ras Harvey rat sarcoma viral oncogene homolog) (eg, Costello syndrome), exon 2 sequence

KCNC3 (potassium voltage-gated channel, Shaw-related subfamily, member 3) (eg, spinocerebellar ataxia), targeted sequence analysis (eg, exon 2)

KCNJ2 (potassium inwardly-rectifying channel, subfamily J, member 2) (eg, Andersen-Tawil syndrome), full gene sequence

KCNJ11 (potassium inwardly-rectifying channel, subfamily J, member 11) (eg, familial hyperinsulinism), full gene sequence

Killer cell immunoglobulin-like receptor (KIR) gene family (eg, hematopoietic stem cell transplantation), genotyping of KIR family genes

Known familial variant not otherwise specified, for gene listed in Tier 1 or Tier 2, or identified during a genomic sequencing procedure, DNA sequence analysis, each variant exon

(For a known familial variant that is considered a common variant, use specific common variant Tier 1 or Tier 2 code)

MC4R (melanocortin 4 receptor) (eg, obesity), full gene sequence

MICA (MHC class I polypeptide-related sequence A) (eg, solid organ transplantation), common variants (eg, *001, *002)

MT-RNR1 (mitochondrially encoded 12S RNA) (eg, nonsyndromic hearing loss), full gene sequence

MT-TS1 (mitochondrially encoded tRNA serine 1) (eg, nonsyndromic hearing loss), full gene sequence

NDP (Norrie disease [pseudoglioma]) (eg, Norrie disease), duplication/deletion analysis

NHLRC1 (NHL repeat containing 1) (eg, progressive myoclonus epilepsy), full gene sequence

PHOX2B (paired-like homeobox 2b) (eg, congenital central hypoventilation syndrome), duplication/deletion analysis

PLN (phospholamban) (eg, dilated cardiomyopathy, hypertrophic cardiomyopathy), full gene sequence

RHD (Rh blood group, D antigen) (eg, hemolytic disease of the fetus and newborn, Rh maternal/fetal compatibility), deletion analysis (eg, exons 4, 5, and 7, pseudogene)

RHD (Rh blood group, D antigen) (eg, hemolytic disease of the fetus and newborn, Rh maternal/fetal compatibility), deletion analysis (eg, exons 4, 5, and 7, pseudogene), performed on cell-free fetal DNA in maternal blood

(For human erythrocyte gene analysis of RHD, use a separate unit of 81403)

SH2D1A (SH2 domain containing 1A) (eg, X-linked lymphoproliferative syndrome), duplication/deletion analysis

TWIST1 (twist homolog 1 [Drosophila]) (eg, Saethre-Chotzen syndrome), duplication/deletion analysis

UBA1 (ubiquitin-like modifier activating enzyme 1) (eg, spinal muscular atrophy, X-linked), targeted sequence analysis (eg, exon 15)

VHL (von Hippel-Lindau tumor suppressor) (eg, von Hippel-Lindau familial cancer syndrome), deletion/duplication analysis

VWF (von Willebrand factor) (eg, von Willebrand disease types 2A, 2B, 2M), targeted sequence analysis (eg, exon 28)

© Copyright 2025 American Medical Association. All rights reserved.

Common Language Description

Molecular pathology procedures are specialized tests conducted at the molecular level to diagnose, treat, and provide prognostic indicators for various genetic disorders, cancers, infectious diseases, and to assess tissue histocompatibility in transplant procedures. These procedures are categorized into different levels based on their complexity, which reflects the amount of professional work and laboratory costs involved in performing them. Specifically, Level 4 molecular pathology tests encompass a range of analyses, including the examination of a single exon through DNA sequence analysis, the analysis of more than ten amplicons utilizing multiplex polymerase chain reaction (PCR) across two or more independent reactions, as well as mutation scanning or the identification of duplication/deletion variants affecting two to five exons. The process begins with a thorough review of the patient's medical history, clinical findings, and results from other diagnostic tests and procedures by a molecular pathologist. Following this comprehensive evaluation, the Level 4 test is conducted. This code, CPT® 81403, encompasses a variety of specific Level 4 tests that are explicitly identified. Additionally, any molecular pathology procedures that require a similar level of professional expertise, involve comparable amounts of work and laboratory costs, and utilize similar techniques but lack a more specific code should also be reported using this code. Upon completion of the test, the molecular pathologist interprets the results and generates a detailed written report outlining the findings, which is essential for guiding further clinical decision-making.

© Copyright 2025 Coding Ahead. All rights reserved.

1. Indications

The following conditions and symptoms indicate the necessity for performing the molecular pathology procedures described under CPT® Code 81403:

  • ANG (angiogenin, ribonuclease, RNase A family, 5) - Associated with amyotrophic lateral sclerosis.
  • ARX (aristaless related homeobox) - Related to X-linked lissencephaly with ambiguous genitalia and X-linked intellectual disability.
  • CEL (carboxyl ester lipase [bile salt-stimulated lipase]) - Linked to maturity-onset diabetes of the young (MODY).
  • CTNNB1 (catenin [cadherin-associated protein], beta 1, 88kDa) - Associated with desmoid tumors.
  • DAZ/SRY (deleted in azoospermia and sex determining region Y) - Related to male infertility.
  • DNMT3A (DNA [cytosine-5-]-methyltransferase 3 alpha) - Associated with acute myeloid leukemia.
  • EPCAM (epithelial cell adhesion molecule) - Related to Lynch syndrome.
  • F8 (coagulation factor VIII) - Associated with hemophilia A.
  • F12 (coagulation factor XII [Hageman factor]) - Related to hereditary angioedema and factor XII deficiency.
  • FGFR3 (fibroblast growth factor receptor 3) - Associated with isolated craniosynostosis.
  • GJB1 (gap junction protein, beta 1) - Related to Charcot-Marie-Tooth X-linked disease.
  • GNAQ (guanine nucleotide-binding protein G[q] subunit alpha) - Associated with uveal melanoma.
  • Human erythrocyte antigen gene analyses - Related to conditions such as sickle-cell disease and thalassemia.
  • HRAS (v-Ha-ras Harvey rat sarcoma viral oncogene homolog) - Associated with Costello syndrome.
  • KCNC3 (potassium voltage-gated channel, Shaw-related subfamily, member 3) - Related to spinocerebellar ataxia.
  • KCNJ2 (potassium inwardly-rectifying channel, subfamily J, member 2) - Associated with Andersen-Tawil syndrome.
  • KCNJ11 (potassium inwardly-rectifying channel, subfamily J, member 11) - Related to familial hyperinsulinism.
  • Killer cell immunoglobulin-like receptor (KIR) gene family - Associated with hematopoietic stem cell transplantation.
  • MC4R (melanocortin 4 receptor) - Related to obesity.
  • MICA (MHC class I polypeptide-related sequence A) - Associated with solid organ transplantation.
  • MT-RNR1 (mitochondrially encoded 12S RNA) - Related to nonsyndromic hearing loss.
  • MT-TS1 (mitochondrially encoded tRNA serine 1) - Associated with nonsyndromic hearing loss.
  • NDP (Norrie disease [pseudoglioma]) - Related to Norrie disease.
  • NHLRC1 (NHL repeat containing 1) - Associated with progressive myoclonus epilepsy.
  • PHOX2B (paired-like homeobox 2b) - Related to congenital central hypoventilation syndrome.
  • PLN (phospholamban) - Associated with dilated cardiomyopathy and hypertrophic cardiomyopathy.
  • RHD (Rh blood group, D antigen) - Related to hemolytic disease of the fetus and newborn.
  • SH2D1A (SH2 domain containing 1A) - Associated with X-linked lymphoproliferative syndrome.
  • TWIST1 (twist homolog 1 [Drosophila]) - Related to Saethre-Chotzen syndrome.
  • UBA1 (ubiquitin-like modifier activating enzyme 1) - Associated with spinal muscular atrophy, X-linked.
  • VHL (von Hippel-Lindau tumor suppressor) - Related to von Hippel-Lindau familial cancer syndrome.
  • VWF (von Willebrand factor) - Associated with von Willebrand disease types 2A, 2B, and 2M.

2. Procedure

The procedure for molecular pathology under CPT® Code 81403 involves several detailed steps, which are outlined as follows:

  • Step 1: Patient Evaluation - The molecular pathologist begins by reviewing the patient's medical history and clinical findings. This includes gathering information from previous diagnostic tests and procedures to understand the context of the patient's condition.
  • Step 2: Selection of Test - Based on the evaluation, the appropriate Level 4 molecular pathology test is selected. This may involve analyzing a single exon through DNA sequence analysis, conducting multiplex PCR for more than ten amplicons, or performing mutation scanning or duplication/deletion analysis of two to five exons.
  • Step 3: Sample Preparation - The laboratory prepares the biological sample, which may include blood, tissue, or other specimens, ensuring that it is suitable for the specific molecular analysis to be performed.
  • Step 4: Performing the Test - The selected molecular pathology procedure is conducted in the laboratory. This may involve advanced techniques such as DNA sequencing, PCR amplification, or other molecular assays to detect genetic variants or abnormalities.
  • Step 5: Data Analysis - After the test is completed, the results are analyzed. This includes interpreting the data obtained from the molecular tests to identify any genetic mutations, duplications, or deletions relevant to the patient's condition.
  • Step 6: Reporting Results - Finally, the molecular pathologist compiles the findings into a detailed written report. This report outlines the results of the analysis, any identified genetic variants, and their potential implications for the patient's diagnosis and treatment.

3. Post-Procedure

Following the completion of the molecular pathology procedure, the molecular pathologist provides a comprehensive report detailing the findings. This report is crucial for guiding further clinical decision-making and may influence treatment options or additional testing. Patients may be advised on the next steps based on the results, which could include further diagnostic evaluations, consultations with specialists, or monitoring for specific conditions. The molecular pathologist may also discuss the implications of the findings with the referring physician to ensure a coordinated approach to patient care.

Short Descr MOPATH PROCEDURE LEVEL 4
Medium Descr MOLECULAR PATHOLOGY PROCEDURE LEVEL 4
Long Descr Molecular pathology procedure, Level 4 (eg, analysis of single exon by DNA sequence analysis, analysis of >10 amplicons using multiplex PCR in 2 or more independent reactions, mutation scanning or duplication/deletion variants of 2-5 exons) ANG (angiogenin, ribonuclease, RNase A family, 5) (eg, amyotrophic lateral sclerosis), full gene sequence ARX (aristaless related homeobox) (eg, X-linked lissencephaly with ambiguous genitalia, X-linked intellectual disability), duplication/deletion analysis CEL (carboxyl ester lipase [bile salt-stimulated lipase]) (eg, maturity-onset diabetes of the young [MODY]), targeted sequence analysis of exon 11 (eg, c.1785delC, c.1686delT) CTNNB1 (catenin [cadherin-associated protein], beta 1, 88kDa) (eg, desmoid tumors), targeted sequence analysis (eg, exon 3) DAZ/SRY (deleted in azoospermia and sex determining region Y) (eg, male infertility), common deletions (eg, AZFa, AZFb, AZFc, AZFd) DNMT3A (DNA [cytosine-5-]-methyltransferase 3 alpha) (eg, acute myeloid leukemia), targeted sequence analysis (eg, exon 23) EPCAM (epithelial cell adhesion molecule) (eg, Lynch syndrome), duplication/deletion analysis F8 (coagulation factor VIII) (eg, hemophilia A), inversion analysis, intron 1 and intron 22A F12 (coagulation factor XII [Hageman factor]) (eg, angioedema, hereditary, type III; factor XII deficiency), targeted sequence analysis of exon 9 FGFR3 (fibroblast growth factor receptor 3) (eg, isolated craniosynostosis), targeted sequence analysis (eg, exon 7) (For targeted sequence analysis of multiple FGFR3 exons, use 81404) GJB1 (gap junction protein, beta 1) (eg, Charcot-Marie-Tooth X-linked), full gene sequence GNAQ (guanine nucleotide-binding protein G[q] subunit alpha) (eg, uveal melanoma), common variants (eg, R183, Q209) Human erythrocyte antigen gene analyses (eg, SLC14A1 [Kidd blood group], BCAM [Lutheran blood group], ICAM4 [Landsteiner-Wiener blood group], SLC4A1 [Diego blood group], AQP1 [Colton blood group], ERMAP [Scianna blood group], RHCE [Rh blood group, CcEe antigens], KEL [Kell blood group], DARC [Duffy blood group], GYPA, GYPB, GYPE [MNS blood group], ART4 [Dombrock blood group]) (eg, sickle-cell disease, thalassemia, hemolytic transfusion reactions, hemolytic disease of the fetus or newborn), common variants HRAS (v-Ha-ras Harvey rat sarcoma viral oncogene homolog) (eg, Costello syndrome), exon 2 sequence KCNC3 (potassium voltage-gated channel, Shaw-related subfamily, member 3) (eg, spinocerebellar ataxia), targeted sequence analysis (eg, exon 2) KCNJ2 (potassium inwardly-rectifying channel, subfamily J, member 2) (eg, Andersen-Tawil syndrome), full gene sequence KCNJ11 (potassium inwardly-rectifying channel, subfamily J, member 11) (eg, familial hyperinsulinism), full gene sequence Killer cell immunoglobulin-like receptor (KIR) gene family (eg, hematopoietic stem cell transplantation), genotyping of KIR family genes Known familial variant not otherwise specified, for gene listed in Tier 1 or Tier 2, or identified during a genomic sequencing procedure, DNA sequence analysis, each variant exon (For a known familial variant that is considered a common variant, use specific common variant Tier 1 or Tier 2 code) MC4R (melanocortin 4 receptor) (eg, obesity), full gene sequence MICA (MHC class I polypeptide-related sequence A) (eg, solid organ transplantation), common variants (eg, *001, *002) MT-RNR1 (mitochondrially encoded 12S RNA) (eg, nonsyndromic hearing loss), full gene sequence MT-TS1 (mitochondrially encoded tRNA serine 1) (eg, nonsyndromic hearing loss), full gene sequence NDP (Norrie disease [pseudoglioma]) (eg, Norrie disease), duplication/deletion analysis NHLRC1 (NHL repeat containing 1) (eg, progressive myoclonus epilepsy), full gene sequence PHOX2B (paired-like homeobox 2b) (eg, congenital central hypoventilation syndrome), duplication/deletion analysis PLN (phospholamban) (eg, dilated cardiomyopathy, hypertrophic cardiomyopathy), full gene sequence RHD (Rh blood group, D antigen) (eg, hemolytic disease of the fetus and newborn, Rh maternal/fetal compatibility), deletion analysis (eg, exons 4, 5, and 7, pseudogene) RHD (Rh blood group, D antigen) (eg, hemolytic disease of the fetus and newborn, Rh maternal/fetal compatibility), deletion analysis (eg, exons 4, 5, and 7, pseudogene), performed on cell-free fetal DNA in maternal blood (For human erythrocyte gene analysis of RHD, use a separate unit of 81403) SH2D1A (SH2 domain containing 1A) (eg, X-linked lymphoproliferative syndrome), duplication/deletion analysis TWIST1 (twist homolog 1 [Drosophila]) (eg, Saethre-Chotzen syndrome), duplication/deletion analysis UBA1 (ubiquitin-like modifier activating enzyme 1) (eg, spinal muscular atrophy, X-linked), targeted sequence analysis (eg, exon 15) VHL (von Hippel-Lindau tumor suppressor) (eg, von Hippel-Lindau familial cancer syndrome), deletion/duplication analysis VWF (von Willebrand factor) (eg, von Willebrand disease types 2A, 2B, 2M), targeted sequence analysis (eg, exon 28)
Status Code Statutory Exclusion (from MPFS, may be paid under other methodologies)
Global Days XXX - Global Concept Does Not Apply
PC/TC Indicator (26, TC) 9 - Not Applicable
Multiple Procedures (51) 9 - Concept does not apply.
Bilateral Surgery (50) 9 - Concept does not apply.
Physician Supervisions 09 - Concept does not apply.
Assistant Surgeon (80, 82) 9 - Concept does not apply.
Co-Surgeons (62) 9 - Concept does not apply.
Team Surgery (66) 9 - Concept does not apply.
Diagnostic Imaging Family 99 - Concept Does Not Apply
CLIA Waived (QW) No
APC Status Indicator Service Paid under Fee Schedule or Payment System other than OPPS
Type of Service (TOS) 5 - Diagnostic Laboratory
Berenson-Eggers TOS (BETOS) T1H - Lab tests - other (non-Medicare fee schedule)
MUE 4
CCS Clinical Classification 234 - Pathology
90 Reference (outside) laboratory: when laboratory procedures are performed by a party other than the treating or reporting physician or other qualified health care professional, the procedure may be identified by adding modifier 90 to the usual procedure number.
59 Distinct procedural service: under certain circumstances, it may be necessary to indicate that a procedure or service was distinct or independent from other non-e/m services performed on the same day. modifier 59 is used to identify procedures/services, other than e/m services, that are not normally reported together, but are appropriate under the circumstances. documentation must support a different session, different procedure or surgery, different site or organ system, separate incision/excision, separate lesion, or separate injury (or area of injury in extensive injuries) not ordinarily encountered or performed on the same day by the same individual. however, when another already established modifier is appropriate it should be used rather than modifier 59. only if no more descriptive modifier is available, and the use of modifier 59 best explains the circumstances, should modifier 59 be used. note: modifier 59 should not be appended to an e/m service. to report a separate and distinct e/m service with a non-e/m service performed on the same date, see modifier 25.
GA Waiver of liability statement issued as required by payer policy, individual case
26 Professional component: certain procedures are a combination of a physician or other qualified health care professional component and a technical component. when the physician or other qualified health care professional component is reported separately, the service may be identified by adding modifier 26 to the usual procedure number.
XU Unusual non-overlapping service, the use of a service that is distinct because it does not overlap usual components of the main service
91 Repeat clinical diagnostic laboratory test: in the course of treatment of the patient, it may be necessary to repeat the same laboratory test on the same day to obtain subsequent (multiple) test results. under these circumstances, the laboratory test performed can be identified by its usual procedure number and the addition of modifier 91. note: this modifier may not be used when tests are rerun to confirm initial results; due to testing problems with specimens or equipment; or for any other reason when a normal, one-time, reportable result is all that is required. this modifier may not be used when other code(s) describe a series of test results (eg, glucose tolerance tests, evocative/suppression testing). this modifier may only be used for laboratory test(s) performed more than once on the same day on the same patient.
AQ Physician providing a service in an unlisted health professional shortage area (hpsa)
GW Service not related to the hospice patient's terminal condition
GY Item or service statutorily excluded, does not meet the definition of any medicare benefit or, for non-medicare insurers, is not a contract benefit
GZ Item or service expected to be denied as not reasonable and necessary
XS Separate structure, a service that is distinct because it was performed on a separate organ/structure
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