Molecular Pathology 2012 CPT Changes

Molecular Pathology 2012 CPT Changes

[WARNING: See chapter 12 before using the new Molecular Pathology codes 81200-81408;

**Medicare has not yet approved these codes for payment in calendar year 2012.**

Molecular pathology procedures are medical laboratory procedures involving the analyses of nucleic acid to detect variants in genes that may be indicative of germline (e.g. constitutional disorders) or somatic (e.g. neoplasia) conditions, or to test for histocompatibility antigens (e.g. HLA). Code selection is typically based on the specific gene(s) that is being analyzed. Genes are described using Human Genome Organization (HUGO) approved gene names and are italicized in the code descriptors. Gene names were taken from tables of the HUGO Gene Nomenclature Committee (HGNC) at the time the CPT codes were developed. For the most part, Human Genome Variation Society (HGVS) recommendations were followed for the names of specific molecular variants. The familiar name is used for some variants because defined criteria were not in place when the variant was first described or because HGVS recommendations were changed over time (e.g. intronic variants, processed proteins). When the gene name is represented by an abbreviation, the abbreviation is listed first, followed by the full gene name italicized in parentheses (e.g. “F5 [coagulation Factor V]”), except for the HLA series of codes. Proteins or diseases commonly associated with the genes are listed as examples in the code descriptors. The examples do not represent all conditions in which testing of the gene may be indicated.

Codes that describe tests to assess for the presence of gene variants (see definitions) use common gene variant names. Typically, all of the listed variants would be tested. However, these lists are not exclusive. If other variants are also tested in the analysis, they would be included in the procedure and not reported separately. Full gene sequencing should not be reported using codes that assess for the presence of gene variants unless specifically stated in the code descriptor.

The molecular pathology codes include all analytical services performed in the test (e.g. cell lysis, nucleic acid stabilization, extraction, digestion, amplification, and detection). Any procedures required prior to cell lysis (e.g. microdissection, codes 88380 and 88381) should be reported separately.

The results of the procedure may require interpretation by a physician or other qualified healthcare professional. When only the interpretation and report are performed, modifier 26 may be appended to the specific molecular pathology code.

[WARNING: Government payers and most private insurers will not knowingly pay for an “interpretation” made by other than a physician; therefore, you should ignore the AMA advice to bill a molecular pathology code with modifier

26 appended for a service by an “other qualified health care professional.”]

All analyses are qualitative unless otherwise noted.

For microbial identification, see 87149-87153 and 87470-87801, and 87900-87904. For in situ hybridization analyses, see 88271-88275 and 88365-88368.

Molecular pathology procedures that are not specified in 81200-81383 should be reported usingeither the appropriate Tier 2 code (81400-81408) or the appropriate methodology codes in the 83890-83914 and 88384-88386 series.

For purposes of CPT reporting, the following definitions apply:

Abnormal allele: an alternative form of a gene that contains a disease-related variation from the normal sequence.

Breakpoint: the region at which a chromosome breaks during a translocation (defined elsewhere). These regions are often consistent for a given translocation.

Codon: a discrete unit of three nucleotides of a DNA or mRNA sequence that encodes a specific amino acid within, or signals the termination of, a polypeptide.

Common variants: variants (as defined elsewhere) that are associated with compromised gene function and are interrogated in a single round of laboratory testing (in a single, typically multiplex, assay format or using more than one assay to encompass all variants to be tested).

These variants typically fit the definition of a “mutation,” and are usually the predominant ones causing disease. Testing for additional uncommon variants may provide additional limited value in assessment of a patient. Often there are professional society recommendations or guidelines for which variants are most appropriate to test (e.g. American College of Medical Genetics, American

College of Obstetrics and Gynecology guidelines for variants used in population screening for cystic fibrosis.

Constitutional: synonymous with germline, often used in reference to the genetic code that is present at birth.

Cytogenomic: chromosome analysis using molecular techniques.

Duplication/Deletion (Dup/Del): terms thatare usually used together with the ‘/’ to refer tomolecular testing, which assesses the dosage of a particular genomic region. The region tested is typically of modest to substantial size—from several dozen to several million or more nucleotides. Normal gene dosage is two copies per cell, except for the sex chromosomes (X and Y). Thus, zero or one copy represents a deletion, and three (or more) copies represent a duplication.

Dynamic mutation: polynucleotide (e.g. trinucleotide) repeats that are in or associated with genes that can undergo disease-producing increases or decreases in the numbers of repeats within tissues and across generations.

Exon: typically, one of multiple nucleic acid sequences used to encode information for a gene product (polypeptide or protein). Exons are separated from each other by non-protein-coding sequences known as introns. Exons at the respective ends of a gene also contain nucleic acid sequence that does not code for the gene’s protein product.

Gene: a nucleic acid sequence that typically contains information for coding a protein as well as for the regulated expression of that protein. Human genes usually contain multiple protein coding regions (exons) separated by non-protein coding regions (introns). See also exon, intron, and polypeptide.

Intron: a nucleic acid sequence found between exons in human genes. An intron contains essential sequences for its proper removal (by a process known as splicing) to join exon together and thus facilitate production of a functional protein from a gene. An intron is sometimes referred to as an intervening sequence (IVS).

Microarray: surface(s) on which multiple specific nucleic acid sequences are attached in a known arrangement. Sometimes referred to as a ‘gene chip’. Examples of uses of microarrays include evaluation of a patient specimen for gains or losses of DNA sequences (copy number variants, CNVs), identification of the presence of specific nucleotide sequence variants (also known as single nucleotide polymorphisms, SNPs), mRNA expression levels, or DNA sequence analysis.

Mutations: typically are variants associated with altered gene function that lead to functional deficits or disease (pathogenic).

Mutation scanning: a technique (e.g. single strand conformation polymorphism, temperature gradient gel electrophoresis, etc.) typically employed on multiple PCR amplicons to indicate the presence of DNA sequence variants by differences in physical properties compared to normal. Variants are then further characterized by DNA sequence analysis only in amplicons which demonstrate differences.

Polymorphisms: typically are variants that do not compromise gene function or produce disease (benign).

Polypeptide: a sequence of amino acids covalently linked in a specified order. Polypeptides alone or in combination with other polypeptide subunits are the building blocks of proteins.

Short Tandem Repeat (STR): a region of DNA where a pattern of two or more nucleotides are repeated. The number of repeating segments can be used as genetic markers for human identity testing.

Single-nucleotide polymorphism (SNP): a DNA sequence variation existing at a significant frequency in the population, in which a single nucleotide (A, T, C, or G) differs between individuals and/or within an individual’s paired chromosomes.

Somatic: synonymous with acquired, referring to genetic code alterations that develop after birth (e.g. occurring in neoplastic cells).

Translocation: an abnormality resulting from the breakage of a chromosome and the relocation of a portion of that chromosome’s DNA sequence to the same or another chromosome. Most common translocations involve a reciprocal exchange of DNA sequences between two differently numbered (i.e. non-homologous) chromosomes, with or without a clinically significant loss of DNA.

Variant: a nucleotide sequence difference from the “normal” (predominant) sequence for a given region.

Variants are typically of two types: substitutions of one nucleotide for another, and deletions or insertions of nucleotides.

Occasionally, variants reflect several nucleotide sequence changes in reasonably close proximity on the same chromosomal strand of DNA (a haplotype).

These nucleotide sequence variants often result in amino acid changes in the protein made by the gene. The term variant does not itself carry a functional implication for those protein changes.

Variants in introns are typically described in one of two ways.

The altered nucleotide(s) within a defined intervening sequence (e.g. IVS3-2A>G) of a gene is listed with a “+” or “-” sign, which indicates the position relative to the first or last nucleotide of the intron.

Or,

The variant position is indicated relative to the last nucleotide of the preceding exon or first nucleotide of the following exon (e.g. c.171+1G>A c.172-1G>T are single nucleotide changes at the first and last nucleotide of a given intron for a specific gene).

The majority of the variants described here are listed by the amino acid change using the single letter amino acid code for the original amino acid followed by the numerical position in the protein product and the amino acid substitution, e.g., for ASPA E285A, Glutamic acid (E) at position 285 is replaced with an alanine (A). A few of the variants are described by the DNA change using the numerical position followed by the original nucleotide, a greater than sign (>) and the new nucleotide, e.g. MTHFR.677C>T.

A known familial variant is a specific mutation that has previously been identified within a patient’s family.

Tier 1 Molecular Pathology Procedures

The following codes represent gene-specific and genomic procedures:

81200 ASPA (aspartoacylase) (e.g., Canavan disease) gene analysis, common variants (e.g. E285A, Y231X)

81205 BCKDHB (branched-chain keto acid dehydrogenase E1, beta polypeptide) (e.g., Maple syrup urine disease) gene analysis, common variants (e.g. R183P, G278S, E422X)

81206 BCR/ABL1 (t (9;22)) (e.g., chronic myelogenous leukemia) translocation analysis; major breakpoint, qualitative or quantitative

81207 minor breakpoint, qualitative or quantitative

81208 other breakpoint, qualitative or quantitative

81209 BLM (Bloom syndrome, RecQ helicase-like) (e.g., Bloom syndrome) gene analysis, 2281del6ins7 variant

81210 BRAF (v-raf murine sarcoma viral oncogene homolog B1) (e.g., colon cancer), gene analysis, V600E variant

81211 BRCA1, BRCA2 (breast cancer 1 and 2) (e.g. hereditary breast and ovarian cancer) gene analysis; full sequence analysis and common duplication/deletion variants in BRCA1 (i.e., exon 13 del 3.835kb, exon 13 dup 6kb, exon 14-20 del 26kb, exon 22 del 510bp, exon 8-9 del 7.1kb)

81212 185delAG, 5385insC, 6174delT variants

81213 uncommon duplication/deletion variants

81214 BRCA1 (breast cancer 1) (e.g., hereditary breast and ovarian cancer) gene analysis; full sequence analysis and common duplication/deletion variants (i.e. exon 13 del 3.835kb, exon 13 dup 6kb, exon 14-20 del 26kb, exon 22 del 510bp, exon 8-9 del 7.1kb) (When performing BRCA1 full sequence analysis with BRAC2 full sequence analysis, use 81211)

81215 known familial variant

81216 BRCA2 (breast cancer 2) (e.g., hereditary breast and ovarian cancer) gene analysis; full sequence analysis (When performing BRCA2 full sequence analysis with BRCA1 full sequence analysis, use 81211)

81217 known familial variant

81220 CFTR (cystic fibrosis transmembrane conductance regulator) (e.g., cystic fibrosis) gene analysis; common variants (e.g. ACMG/ACOG guidelines) (When intron 8 poly-T analysis is performed in conjunction with 81220 in a R117H positive patient, do not report 81224)

81221 known familial variants

81222 duplication/deletion variants

81223 full gene sequence

81224 intron 8 poly-T analysis (e.g. male infertility)

81225 CYP2C19 (cytochrome P450, family 2, subfamily C, polypeptide 19) (e.g. drug metabolism), gene analysis, common variants (e.g. *2, *3, *4, *8, *17)

81226 CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) (e.g. drug metabolism), gene analysis, common variants (e.g. *2, *3, *4, *5, *6, *9, *10, *17, *19, *29, *35, *41, *1XN, *2XN, *4XN)

81227 CYP2C9 (cytochrome P450, family 2, subfamily C, polypeptide 9) (e.g. drug metabolism), gene analysis, common variants (e.g. *2, *3, *5, *6)

81228 Cytogenomic constitutional (genome-wide) microarray analysis; interrogation ofgenomic regions for copy number variants (e.g. Bacterial Artificial Chromosome [BAC] or oligo-based comparative genomic hybridization [CGH] microarray analysis)

81229 interrogation of genomic regions for copy number and single nucleotide polymorphism (SNP) variants for chromosomal abnormalities (Do not report 81228 in conjunction with 81229)

81240 F2 (prothrombin, coagulation factor II) (e.g. hereditary hypercoagulability) gene analysis, 20210G>A variant

81241 F5 (coagulation Factor V) (e.g. hereditary hypercoagulability) gene analysis, Leiden variant

81242 FANCC (Fanconi anemia, complementation group C) (e.g. Fanconi anemia, type C) gene analysis, common variant (e.g. IVS4+4A>T)

81243 FMR1 (Fragile X mental retardation 1) (e.g. fragile X mental retardation) gene analysis; evaluation to detect abnormal (e.g. expanded) alleles (For evaluation to detect and characterize abnormal alleles, see 81243, 81244) (For evaluation to detect and characterize abnormal alleles using a single assay [e.g. PCR], use 81243)

81244 characterization of alleles (e.g. expanded size and methylation status)

81245 FLT3 (fms-related tyrosine kinase 3) (e.g. acute myeloid leukemia), gene analysis, internal tandem duplication (ITD) variants (i.e. exons 14, 15)

81250 G6PC (glucose-6-phosphatase, catalytic subunit) (e.g. Glycogen storage disease, Type 1a, von Gierke disease) gene analysis, common variants (e.g. R83C, Q347X)

81251 GBA (glucosidase, beta, acid) (e.g. Gauche disease) gene analysis, common variants (e.g. N370S, 84GG, L444P, IVS2+1G>A)

81255 HEXA (hexosaminidase A [alpha polypeptide]) (e.g. Tay-Sachs disease) gene analysis, common variants (e.g. 1278insTATC, 1421+1G>C, G269S)

81256 HFE (hemochromatosis) (e.g., hereditary hemochromatosis) gene analysis, common variants (e.g., C282Y, H63D)

81257 HBA1/HBA2 (alpha globin 1 and alpha globin 2) (e.g., alpha thalassemia, Hb Bart hydrops fetalis syndrome, HbH disease), gene analysis, for common deletions or variant (e.g., Southeast Asian, Thai, Filipino, Mediterranean, alpha3.7, alpha4.2, alpha20.5, and Constant Spring)

81260 IKBKAP (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase complexassociated protein) (e.g. familial dysautonomial) gene analysis, common variants (e.g. 2507+6T>C, R696P)

81261 IGH@ (Immunoglobulin heavy chain locus) (e.g. leukemia and lymphoma, B-cell), gene rearrangement analysis to detect abnormal clonal population(s); amplified methodology (e.g., polymerase chain reaction)

81262 direct probe methodology (e.g., Southern blot)

81263 IGH@ (Immunoglobulin heavy chain locus) (e.g., leukemia and lymphoma, B-cell), variable region somatic mutation analysis

81264 IGK@ (Immunoglobulin kappa light chain locus) (e.g. leukemia and lymphoma, B-cell) gene rearrangement analysis, evaluation to detect abnormal clonal population(s) (For immunoglobulin lambda gene [IGL@] rearrangement or immunoglobulin kappa deleting element [IGKDEL] analysis, report the appropriate methodology code[s] in the 83890-83914 series)

81265 Comparative analysis using Short Tandem Repeat (STR) markers; patient and comparative specimen (e.g. pre-transplant recipient and donor germline testing, posttransplant non-hematopoietic recipient germline [e.g. buccal swab or other germline tissue sample] and donor testing, twin zygosity testing, or maternal cell contamination of fetalcells)

81266 each additional specimen (e.g. additional cord blood donor, additional fetal samples from different cultures, or additional zygosity in multiple birth pregnancies) (List separately in addition to code for primary procedure)(Use 81266 in conjunction with 81265)

81267 Chimerism (engraftment) analysis, post transplantation specimen (e.g. hematopoietic stem cell), includes comparison to previously performed baseline analyses; without cell selection

81268 with cell selection (e.g. CD3, CD33), each cell type (If comparative STR analysis of recipient [using buccal swab or other germline tissue sample] and donor are performed after hematopoietic stem cell transplantation, report 81265, 81266 in conjunction with 81267, 81268 for chimerism testing)

81270 JAK2 (Janus kinase 2) (e.g. myeloproliferative disorder) gene analysis, p.Val617Phe (V617F) variant

81275 KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene) (e.g. carcinoma) gene analysis, variants to codons 12 and 13

81280 Long QT syndrome gene analyses (e.g. KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP, SNTA1, and ANK2); full sequence analysis

81281 known familial sequences variant

81282 duplication/deletion variants

81290 MCOLN1 (mucolipin 1) (e.g. Mucolipidosis, type IV) gene analysis, common variants (e.g. IVS3-2A>G, del6.4kb)

81291 MTHFR (5, 10-methylenetetrahydrofolate reductase) (e.g. hereditary hypercoagulability) gene analysis, common variants (e.g. 677T, 1298C)

81292 MLH1 (mutL homolog 1, colon cancer, non-polyposis type 2) (e.g. hereditary nonpolyposis colorectal cancer, Lynch syndrome) gene analysis; full sequence analysis

81293 known familial variants

81294 duplication/deletion variants

81295 MSH2 (mutS homolog 2, colon cancer, non-polyposis type 1) (e.g. hereditary nonpolyposis colorectal cancer, Lynch syndrome) gene analysis; full sequence analysis

81296 known familial variants

81297 duplication/deletion variants

81298 MSH6 (mutS homolog 6 [E. coli]) (e.g. hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; full sequence analysis

81299 known familial variants

81300 duplication/deletion variants

81301 Microsatellite instability analysis (e.g. hereditary non-polyposis colorectal cancer, Lynch syndrome) of markers for mismatch repair deficiency (e.g. BAT25, BAT26), includes comparison of neoplastic and normal tissue, if performed

81302 MECP2 (methyl CpG binding protein 2) (e.g. Rett syndrome) gene analysis; full sequence analysis

81303 known familial variant s

81304 duplication/deletion variants

81310 NPM1 (nucleophosmin) (e.g. acute myeloid leukemia) gene analysis, exon 12 variants

81315 PML/RARalpha, (t (15; 17), (promyelocytic leukemia/retinoic acid receptor alpha) (e.g. promyelocytic leukemia) translocation analysis; common breakpoints (e.g. intron 3 and intron 6), qualitative or quantitative

81316 single breakpoint (e.g. intron 3, intron 6 or exon 6), qualitative or quantitative (For intron 3 and intron 6 [including exon 6 if performed] analysis, use 81315) (If both intron 6 and exon 6 are analyzed, without intron 3, use one unit of 81316)

81317 PMS2 (postmeiotic segregation increased 2 [S. cerevisiae]) (e.g. hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; full sequence analysis

81318 known familial variants

81319 duplication/deletion variants

81330 SMPD1 (sphingomyelin phosphodiesterase 1, acid lysomal) (e.g. Niemann-Pick disease, Type A) gene analysis, common variants (e.g. R496L, L302P, fsP330)

81331 SNRPN/UBE3A (small nuclear ribonucleoprotein polypeptide N and ubiquitin protein ligase E3A) (e.g. Prader-Willi syndrome and/or Angelman syndrome), methylation analysis

81332 SERPINA1 (serpin peptidase inhibitor, clade A, alpha-1 antiproteinase, antitrypsin, member 1) (e.g. alpha-1-antitrypsin deficiency), gene analysis, common variants (e.g. *S and *Z)

81340 TRB@ (T cell antigen receptor, beta) (e.g. leukemia and lymphoma), gene rearrangement analysis to detect abnormal clonal population(s); using amplification methodology (e.g. polymerase chain reaction)

81341 using direct probe methodology (e.g. Southern blot)

81342 TRG@ (T cell antigen receptor, gamma) (e.g. leukemia and lymphoma), gene rearrangement analysis, evaluation to detect abnormal clonal population(s) (For T cell antigen alpha [TRA@] gene rearrangement analysis, report the appropriate methodology code(s) in the 83890-83914 series) (For T cell antigen delta [TRD@] gene rearrangement analysis, report 81402)

81350 UGT1A1 (UDP glucuronosyltransferase 1 family, polypeptide A1) (e.g. irinotecan metabolism), gene analysis, common variants (e.g. *28, *36, *37)

81355 VKORC1 (vitamin K epoxide reductase complex, subunit 1) (e.g. warfarin metabolism), gene analysis, common variants (e.g. -1639/3673)

Human Leukocyte Antigen (HLA) typing is performed to assess compatibility of recipients and potential donors as a part of solid organ and hematopoietic stem cell pre-transplant testing. HLA testing is also performed to identify HLA alleles and allele groups (antigen equivalents) associated with specific diseases and individualized responses to drug therapy (e.g. HLA-B*27 and ankylosing spondylitis and HLA-B*57:01 and abacavir hypersensitivity), as well as other clinical uses. One or more HLA genes may be tested in specific clinical situations (e.g. HLADQB1 for narcolepsy and HLA-A, -B, -C, -DRB1 and -DQB1 for kidney transplantation). Each HLA gene typically has multiple variant alleles or allele groups that can be identified by typing.

For HLA result reporting, a low resolution HLA type is denoted by a two digit HLA name (e.g. A*02) and intermediate resolution typing by a string of alleles or an NMDP (National Marrow Donor Program) code (e.g. B*14:01/07N/08/12/14, B*39CKGN).

Both low and intermediate resolution are considered low resolution for code assignment. High resolution typing resolves the common well defined (CWD) alleles and is usually denoted by at least 4 digits (e.g. A*02:02, *03:01:01:01, A*26:01:01G, and C*03:04P), however, high resolution typing may include some ambiguities for rare alleles, which may be reported as a string of alleles or an NMDP code.

If additional testing is required to resolve ambiguous allele combinations for high resolution typing, this is included in the base HLA typing codes below.

The gene names have been italicized similar to the other molecular pathology codes.

(For HLA antigen typing by non-molecular pathology techniques, see 86812-86822)

81370 HLA Class I and II typing, low resolution (e.g. antigen equivalents); HLA-A, -B, -C, -DRB1/3/4/5, and -DQB1

81371 HLA-A, -B, and -DRB1/3/4/5 (e.g. verification typing)

81372 HLA Class I typing, low resolution (e.g. antigen equivalents); complete (i.e. HLA-A, -B and -C) (When performing both Class I and II low resolution HLA typing for HLA-A, -B, -C, -DRB1/3/4/5, and -DQB1, use 81370)

81373 one locus (e.g. HLA-A, -B, or -C), each (When performing a complete Class I [HLA-A, -B and -C] low resolution HLA typing, use 81372) (When the presence or absence of a single antigen equivalent is reported using low resolution testing, use 81374)

81374 one antigen equivalent (e.g. B*27), each (When testing for presence or absence of more than 2 antigen equivalents at a locus, use 81373 for each locus tested)

81375 HLA Class II typing, low resolution (e.g. antigen equivalents); HLA-DRB1/3/4/5 and -DQB1(When performing both Class I and II low resolution HLA typing for HLA-A, -B, -C, -DRB1/3/4/5, and -DQB1, use 81370)

81376 one locus (e.g. HLA-DRB1/3/4/5, -DQB1, -DQA1, -DPB1, or -DPA1), each (When low resolution typing is performed for HLA-DRB1/3/4/5 and -DQB1, use 81375) (For low resolution typing, HLA-DRB1/3/4/5 should be treated as a single locus)

81377 one antigen equivalent, each (When testing for presence or absence of more than 2 antigen equivalents at a locus, use 81376 for each locus)

81378 HLA Class I and II typing, high resolution (i.e. alleles or allele groups), HLA-A, -B, -C and -DRB1

81379 HLA Class I typing, high resolution (i.e. alleles or allele groups); complete (i.e. HLA-A, -B, and -C)

81380 one locus (e.g. HLA-A, -B, or -C), each (When a complete Class I high resolution typing for HLA-A, -B, and -C is performed, use 81379) (When the presence or absence of a single allele or allele group is reported using high resolution testing, use 81381)

81381 one allele or allele group (e.g. B*57:01P), each (When testing for the presence or absence of more than 2 alleles or allele groups at a locus, use 81380 for each locus)

81382 HLA Class II typing, high resolution (i.e. alleles or allele groups); one locus (e.g. HLADRB1, -DRB3, -DRB4, -DRB5, -DQB1, -DQA1, -DPB1, or -DPA1), each

(When only the presence or absence of a single allele or allele group is reported using high resolution testing, use 81383)

81383 one allele or allele group (e.g. HLA-DQB1*06:02P), each (When testing for the presence or absence of more than 2 alleles or allele groups at a locus, use 81382 for each locus)

Tier 2 Molecular Pathology Procedures

(Molecular Pathology Tier 2) codes are used to report procedures not listed in the Tier 1 molecular pathology codes (81200- 81383).

They represent medically useful procedures that are generally performed in lower volumes than Tier 1 procedures (e.g. the incidence of the disease being tested is rare).

They are arranged by level of technical resources and interpretive work by the physician or other qualified health care professional. The individual analyses listed under each code (i.e. level of procedure) utilize the definitions and coding principles as described in the introduction preceding the Tier 1

molecular pathology codes. The parenthetical examples of methodologies presented near the beginning of each code provide general guidelines used to group procedures for a given level and are not all-inclusive.

Use the appropriate molecular pathology procedure level code that includes the specific analyte listed after the code descriptor.

If the analyte tested is not listed under one of the Tier 2 codes or

is not represented by a Tier 1 code, use the appropriate methodology codes in the 83890-83914 and 88384-88386 series.

81400 Molecular pathology procedure, Level 1 (e.g. identification of single germline variant [e.g. SNP] by techniques such as restriction enzyme digestion or melt curve analysis):

ACADM (acyl-CoA dehydrogenase, C-4 to C-12 straight chain, MCAD) (e.g. medium chain acyl dehydrogenase deficiency), K304E variant

ACE (angiotensin converting enzyme) (e.g. hereditary blood pressure regulation), insertion/deletion variant

AGTR1 (angiotensin II receptor, type 1) (e.g. essential hypertension), 1166A>C variant

CCR5 (chemokine C-C motif receptor 5) (e.g. HIV resistance), 32-bp deletion mutation/794 825del32 deletion

DPYD (dihydropyrimidine dehydrogenase) (e.g. 5-fluorouracil/5-FU and capecitabine drug metabolism), IVS14+1G>A variant

F2 (coagulation factor 2) (e.g. hereditary hypercoagulability), 1199G>A variant

F5 (coagulation factor V) (e.g. hereditary hypercoagulability), HR2 variant

F7 (coagulation factor VII [serum prothrombin conversion accelerator]) (e.g. hereditary hypercoagulability), R353Q variant

F13B (coagulation factor XIII, B polypeptide) (e.g. hereditary hypercoagulability), V34L variant

FGB (fibrinogen beta chain) (e.g. hereditary ischemic heart disease), -455G>A variant

Human Platelet Antigen 1 genotyping (HPA-1), ITGB3 (integrin, beta 3 [platelet glycoprotein IIIa], antigen CD61 [GPIIIa]) (e.g. neonatal alloimmune thrombocytopenia [NAIT], post-transfusion purpura), HPA-1a/b (L33P)

Human Platelet Antigen 2 genotyping (HPA-2), GP1BA (glycoprotein Ib [platelet], alpha polypeptide [GPIba]) (e.g. neonatal alloimmune thrombocytopenia [NAIT], posttransfusion purpura), HPA-2a/b (T145M)

Human Platelet Antigen 3 genotyping (HPA-3), ITGA2B (integrin, alpha 2b [platelet glycoprotein IIb of IIb/IIIa complex], antigen CD41 [GPIIb]) (e.g. neonatal alloimmune thrombocytopenia [NAIT], post-transfusion purpura), HPA-3a/b (I843S)

Human Platelet Antigen 4 genotyping (HPA-4), ITGB3 (integrin, beta 3 [platelet glycoprotein IIIa], antigen CD61 [GPIIIa]) (e.g. neonatal alloimmune thrombocytopenia [NAIT], post-transfusion purpura), HPA-4a/b (R143Q)

Human Platelet Antigen 5 genotyping (HPA-5), ITGA2 (integrin, alpha 2 [CD49B, alpha2 subunit of VLA-2 receptor] [GPIa]) (e.g. neonatal alloimmune thrombocytopenia [NAIT], post-transfusion purpura), HPA-5a/b (K505E)

Human Platelet Antigen 6 genotyping (HPA-6w), ITGB3 (integrin, beta 3 [platelet glycoprotein IIIa], antigen CD61 [GPIIIa]) (e.g. neonatal alloimmune thrombocytopenia [NAIT], post-transfusion purpura), HPA-6a/b (R489Q)

Human Platelet Antigen 9 genotyping (HPA-9w), ITGA2B (integrin, alpha 2b [platelet glycoprotein IIb of IIb/IIIa complex], antigen CD41] [GPIIb]) (e.g. neonatal alloimmune thrombocytopenia [NAIT], post-transfusion purpura), HPA-9a/b (V837M)

Human Platelet Antigen 15 genotyping (HPA-15), CD109 (CD109 molecule) (e.g. neonatal alloimmune thrombocytopenia [NAIT], post-transfusion purpura), HPA-15a/b (S682Y)

SERPINE1 (serpine peptidase inhibitor clade E, member 1, plasminogen activator inhibitor -1, PAI-1) (e.g. thrombophilia), 4G variant

81401 Molecular pathology procedure, Level 2 (e.g. 2-10 SNPs, 1 methylated variant, or 1 somatic variant [typically using non-sequencing target variant analysis], or detection of a dynamic mutation disorder/triplet repeat:

ABL (c-abl oncogene 1, receptor tyrosine kinase) (e.g. acquired imatinib resistance), T315I variant:

ACADM (acyl-CoA dehydrogenase, C-4 to C-12 straight chain, MCAD) (e.g. medium chain acyl dehydrogenase deficiency), common variants (e.g. K304E, Y42H) ADRB2 (adrenergic beta-2 receptor surface) (e.g. drug metabolism), common variants (e.g. G16R, Q27E)

APOE (apolipoprotein E) (e.g. hyperlipoproteinemia type III, cardiovascular disease, Alzheimer disease), common variants (e.g. *2, *3, *4)

CBFB/MYH11 (inv (16) (e.g. acute myeloid leukemia), qualitative, and quantitative, if performed

CCND1/IGH (BCL1/IgH, t (11; 14)) (e.g. mantle cell lymphoma) translocation analysis, major breakpoint, qualitative, and quantitative, if performed

CFH/ARMS2 (complement factor H/age-related maculopathy susceptibility 2) (e.g. macular degeneration), common variants (e.g. Y402H [CFH], A69S [ARMS2])

CYP3A4 (cytochrome P450, family 3, subfamily A, polypeptide 4) (e.g. drug metabolism), common variants (e.g. *2, *3, *4, *5, *6)

CYP3A5 (cytochrome P450, family 3, subfamily A, polypeptide 5) (e.g. drug metabolism), common variants (e.g. *2, *3, *4, *5, *6)

DMPK (dystrophia myotonica-protein kinase) (e.g. myotonic dystrophy, type 1), evaluation to detect abnormal (e.g. expanded) alleles

F11 (coagulation factor XI) (e.g. coagulation disorder), common variants (e.g. E117X [Type II], F283L [Type III], IVS14del14, and IVS14+1G>A [Type I])

FGFR3 (fibroblast growth factor receptor 3) (e.g. achondroplasia), common variants (e.g. 1138G>A, 1138G>C)

FIP1L1/PDGFRA (del [4q12]) (e.g. imatinib-sensitive chronic eosinophilic leukemia), qualitative, and quantitative, if performed

GALT (galactose-1-phosphate uridylyltransferase) (e.g. galactosemia), common variants (e.g. Q188R, S135L, K285N, T138M, L195P, Y209C, IVS2-2A>G, P171S, del5kb, N314D, L218L/N314D)

HBB (hemoglobin, beta) (e.g. sickle cell anemia, hemoglobin C, hemoglobin E), common variants (e.g. HbS, HbC, HbE)

HTT (huntingtin) (e.g. Huntington disease), evaluation to detect abnormal (e.g. expanded) alleles

RUNX1/RUNX1T1 (t (8; 21)) (e.g. acute myeloid leukemia) translocation analysis, qualitative, and quantitative, if performed SEPT9 (Septin 9) (e.g. colon cancer), methylation analysis TPMT (thiopurine S-methyltransferase) (e.g. drug metabolism), common variants (e.g. *2, *3)

VWF (von Willebrand factor) (e.g. von Willebrand disease type 2N), common variants (e.g. T791M, R816W, R854Q)

81402 Molecular pathology procedure, Level 3 (e.g. >10 SNPs, 2-10 methylated variants, or 2-10 somatic variants [typically using non-sequencing target variant analysis], immunoglobulin and T-cell receptor gene rearrangements, duplication/deletion variants 1 exon):

CYP21A2 (cytochrome P450, family 21, subfamily A, polypeptide 2) (e.g. congenital adrenal hyperplasia, 21-hydroxylase deficiency), common variants (e.g. IVS2-13G, P30L, I172N, exon 6 mutation cluster [I235N, V236E, M238K], V281L, L307FfsX6, Q318X, R356W, P453S, G110VfsX21, 30-kb deletion variant)

ESR1/PGR (receptor 1/progesterone receptor) ratio (e.g. breast cancer)

KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) (e.g. mastocytosis), common variants (e.g. D816V, D816Y, D816F)

MEFV (Mediterranean fever) (e.g. familial Mediterranean fever), common variants (e.g. E148Q, P369S, F479L, M680I, I692del, M694V, M694I, K695R, V726A, A744S, R761H)

MPL (myeloproliferative leukemia virus oncogene, thrombopoietin receptor, TPOR) (e.g. myeloproliferative disorder), common variants (e.g. W515A, W515K, W515L, W515R) TRD@ (T cell antigen receptor, delta) (e.g. leukemia and lymphoma), gene rearrangement analysis, evaluation to detect abnormal clonal population

81403 Molecular pathology procedure, Level 4 (e.g. 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):

ABL1 (c-abl oncogene 1, receptor tyrosine kinase) (e.g. acquired imatinib tyrosine kinase inhibitor resistance), variants in the kinase domain

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

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

JAK2 (Janus kinase 2) (e.g. myeloproliferative disorder), exon 12 sequence and exon 13 sequence, if performed

KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene) (e.g. carcinoma), gene analysis, variant(s) in exon 2

MPL (myeloproliferative leukemia virus oncogene, thrombopoietin receptor, TPOR) (e.g. myeloproliferative disorder), exon 10 sequence

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

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

81404 Molecular pathology procedure, Level 5 (e.g. analysis of 2-5 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of 6-10 exons, or characterization of a dynamic mutation disorder/triplet repeat by Southern blot analysis):

BTD (biotinidase) (e.g. biotinidase deficiency), full gene sequence

CYP1B1 (cytochrome P450, family 1, subfamily B, polypeptide 1) (e.g. primary congenital glaucoma), full gene sequence

DMPK (dystrophia myotonica-protein kinase) (e.g. myotonic dystrophy type 1), characterization of abnormal (e.g. expanded) alleles

EGR2 (early growth response 2) (e.g. Charcot-Marie-Tooth), full gene sequence FKRP (Fukutin related protein) (e.g. congenital muscular dystrophy type 1C [MDC1C], limb-girdle muscular dystrophy [LGMD] type 2I), full gene sequence

FOXG1 (forkhead box G1) (e.g. Rett syndrome), full gene sequence

FSHMD1A (facioscapulohumeral muscular dystrophy 1A) (e.g. facioscapulohumeral muscular dystrophy), evaluation to detect abnormal (e.g. deleted) alleles

FSHMD1A (facioscapulohumeral muscular dystrophy 1A) (e.g. facioscapulohumeral muscular dystrophy), characterization of haplotype(s) (i.e. chromosome 4A and 4B haplotypes)

HBB (hemoglobin, beta, Beta-Globin) (e.g. thalassemia), full gene sequence KIT (C-kit) (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) (e.g. GIST, acute myeloid leukemia, melanoma), targeted gene analysis (e.g. exons 8, 11, 13, 17, 18)

LITAF (lipopolysaccharide-induced TNF factor) (e.g. Charcot-Marie-Tooth), full gene sequence

MEFV (Mediterranean fever) (e.g. familial Mediterranean fever), full gene sequence

NRAS (neuroblastoma RAS viral oncogene homolog) (e.g. colorectal carcinoma), exon 1 and exon 2 sequences

PDGFRA (platelet-derived growth factor receptor alpha polypeptide) (e.g. gastrointestinal stromal tumor), targeted sequence analysis (e.g. exons 12, 18)

RET (ret proto-oncogene) (e.g. multiple endocrine neoplasia, type 2B and familial medullary thyroid carcinoma), common variants (e.g. M918T, 2647-2648delinsTT, A883F)

SDHD (succinate dehydrogenase complex, subunit D, integral membrane protein) (e.g. hereditary paraganglioma), full gene sequence

VHL (von Hippel-Lindau tumor suppressor) (e.g. von Hippel-Lindau familial cancer syndrome), full gene sequence

VWF (von Willebrand factor) (e.g. von Willebrand disease type 1C), targeted sequence analysis (e.g. exons 26, 27, 37)

81405 Molecular pathology procedure, Level 6 (e.g. analysis of 6-10 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of 11-25 exons):

CYP21A2 (cytochrome P450, family 21, subfamily A, polypeptide 2) (e.g. steroid 21- hydroxylase isoform, congenital adrenal hyperplasia), full gene sequence FKTN (fukutin) (e.g. limb-girdle muscular dystrophy [LGMD] type 2M or 2L), full gene sequence

MPZ (myelin protein zero) (e.g. Charcot-Marie-Tooth), full gene sequence

NEFL (neurofilament, light polypeptide) (e.g. Charcot-Marie-Tooth), full gene sequence

RET (ret proto-oncogene) (e.g. multiple endocrine neoplasia, type 2A and familial medullary thyroid carcinoma), targeted sequence analysis (e.g. exons 10, 11, 13-16)

SDHB (succinate dehydrogenase complex, subunit B, iron sulfur) (e.g. hereditary paraganglioma), full gene sequence

TGFBR1 (transforming growth factor, beta receptor 1) (e.g. Marfan syndrome), full gene sequence

TGFBR2 (transforming growth factor, beta receptor 2) (e.g. Marfan syndrome), full gene sequence

THRB (thyroid hormone receptor, beta) (e.g. thyroid hormone resistance, thyroid hormone beta receptor deficiency), full gene sequence or targeted sequence analysis of >5 exons

TP53 (tumor protein 53) (e.g. Li-Fraumeni syndrome, tumor samples), full gene sequence or targeted sequence analysis of >5 exons

VWF (von Willebrand factor) (e.g. von Willebrand disease type 2N), targeted sequence analysis (e.g. exons 18-20, 23-25)

81406 Molecular pathology procedure, Level 7 (e.g. analysis of 11-25 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of 26-50 exons, cytogenomic array analysis for neoplasia):

CAPN3 (Calpain 3) (e.g. limb-girdle muscular dystrophy [LGMD] type 2A, calpainopathy), full gene sequence

Cytogenomic microarray analysis, neoplasia (e.g. interrogation of copy number, and lossof- heterozygosity via single nucleotide polymorphism [SNP]-based comparative genomic hybridization [CGH] microarray analysis)

GALT (galactose-1-phosphate uridylyltransferase) (e.g. galactosemia), full gene sequence

HEXA (hexosaminidase A, alpha polypeptide) (e.g. Tay-Sachs disease), full gene sequence

LMNA (lamin A/C) (e.g. Emery-Dreifuss muscular dystrophy [EDMD1, 2 and 3] limbgirdle muscular dystrophy [LGMD] type 1B, dilated cardiomyopathy [CMD1A], familial partial lipodystrophy [FPLD2]), full gene sequence

PAH (phenylalanine hydroxylase) (e.g. phenylketonuria), full gene sequence

POLG (polymerase [DNA directed], gamma) (e.g. Alpers-Huttenlocher syndrome, autosomal dominant progressive external ophthalmoplegia), full gene sequence

POMGNT1 (protein O-linked mannose beta 1, 2-N acetylglucosaminyltransferase) (e.g. muscle-eye-brain disease, Walker-Warburg syndrome), full gene sequence

POMT1 (protein-O-mannosyltransferase 1) (e.g. limb-girdle muscular dystrophy [LGMD] type 2K, Walker-Warburg syndrome), full gene sequence

POMT2 (protein-O-mannosyltransferase 2) (e.g. limb-girdle muscular dystrophy [LGMD] type 2N, Walker-Warburg syndrome), full gene sequence

RYR1 (ryanodine receptor 1, skeletal) (e.g. malignant hyperthermia), targeted sequence analysis of exons with functionally-confirmed mutation

VWF (von Willebrand factor) (e.g. von Willebrand disease type 2A), extended targeted sequence analysis (e.g. exons 11-16, 24-26, 51, 52)

81407 Molecular pathology procedure, Level 8 (e.g. analysis of 26-50 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of >50 exons, sequence analysis of multiple genes on one platform):

SCN1A (sodium channel, voltage-gated, type 1, alpha subunit) (e.g. generalized epilepsy with febrile seizures), full gene sequence

81408 Molecular pathology procedure, Level 9 (e.g. analysis of >50 exons in a single gene by DNA sequence analysis):

FBN1 (fibrillin 1) (e.g. Marfan syndrome), full gene sequence

NF1 (neurofibromin 1) (e.g. neurofibromatosis, type 1), full gene sequence

RYR1 (ryanodine receptor 1, skeletal) (e.g. malignant hyperthermia), full gene sequence

VWF (von Willebrand factor) (e.g. von Willebrand disease types 1 and 3), full gene Sequence

83020 Hemoglobin fractionation and quantitation; electrophoresis (e.g. A2, S, C, and/or F)

[Molecular Diagnostics “Stacking” Codes]—Codes 83890-83914 are intended for use with molecular diagnostic techniques for analysis of nucleic acids.

Codes 83890-83914 are coded by procedure rather than analyte.

Code separately for each procedure used in an analysis. For example, a procedure requiring isolation of DNA, restriction endonuclease digestion, electrophoresis, and nucleic acid probe amplification would be coded 83890, 83892, 83894, and 83898.

When molecular diagnostic procedures are performed to test for oncology, hematology, neurology or inherited disorder, use the appropriate [genetic testing code] modifier to specify probe type or condition tested.

Each nucleic acid preparation may include a digestate, undigested nucleic acid, or other uniquely modified nucleic acid sample, e.g. newly synthesized oligonucleotide.

(For microbial identification, see 87149, 87150 87152, 87153, 87470-87801)

(For array technology using more than 10 probes, see 88384-88386)

83890 Molecular diagnostics; molecular isolation or extraction, each nucleic acid type (i.e. DNA or RNA)

83891 isolation or extraction of highly purified nucleic acid, each nucleic acid type (i.e. DNA or RNA)

83892 enzymatic digestion, each enzyme treatment

83893 dot/slot blot production, each nucleic acid preparation

83894 separation by gel electrophoresis (e.g. agarose, polyacrylamide), each nucleic acid preparation

83896 nucleic acid probe, each

83897 nucleic acid transfer (e.g. Southern, Northern), each nucleic acid preparation

83898 amplification, target, each nucleic acid sequence

(For multiplex target amplification, see 83900, 83901)

(For signal amplification, use 83908)

83900 amplification, target, multiplex, first two nucleic acid sequences

83901 amplification, target, multiplex, each additional nucleic acid sequence beyond 2 (List separately in addition to code for primary procedure) (Use 83901 in conjunction with 83900)

83902 reverse transcription

83903 mutation scanning, by physical properties (e.g. single strand conformational polymorphisms (SSCP), heteroduplex, denaturing gradient gel electrophoresis (DGGE), RNA′ase A), single segment, each

83904 mutation identification by sequencing, single segment, each segment

83905 mutation identification by allele specific transcription, single segment, each segment

83906 mutation identification by allele specific translation, single segment, each segment

83907 lysis of cells prior to nucleic acid extraction (e.g. stool specimens, paraffin embedded tissue), each specimen

83908 amplification, signal, each nucleic acid sequence (For target amplification, see 83898, 83900, and 83901)

83909 separation and identification by high resolution technique (e.g. capillary electrophoresis), each nucleic acid preparation

83912 interpretation and report

83913 RNA stabilization

83914 Mutation identification by enzymatic ligation or primer extension, single segment, each segment (e.g. oligonucleotide ligation assay (OLA), single base chain extension (SBCE), or allele-specific primer extension (ASPE))