Certified Professional Coder (CPC) Quiz: Code Molecular Pathology Services
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Code Molecular Pathology ServicesQuestion 1 of 20

A laboratory performs EGFR common variant analysis (exon 19 deletions and L858R/T790M) on a non-small cell lung cancer specimen to guide TKI therapy selection. Which CPT® code is reported?

81210
81275
81235
81272
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Certified Professional Coder (CPC) Quiz

Certified Professional Coder (CPC) Quiz: Code Molecular Pathology Services

Practice Code Molecular Pathology Services in Certified Professional Coder (CPC) with focused quiz questions that help you check what you know, review explanations, and build confidence with test-style prompts.

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This quiz focuses on Code Molecular Pathology Services, giving you a quick way to practice the rules, question types, and explanations that matter most for Certified Professional Coder (CPC).

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Question 1

A laboratory performs EGFR common variant analysis (exon 19 deletions and L858R/T790M) on a non-small cell lung cancer specimen to guide TKI therapy selection. Which CPT® code is reported?

  1. 81210
  2. 81275
  3. 81235 (correct answer)
  4. 81272
Explanation: CPT® 81235 describes EGFR (epidermal growth factor receptor) gene analysis for common variants — the correct code for testing EGFR for activating mutations (exon 19 deletions, L858R) and resistance mutations (T790M) that guide tyrosine kinase inhibitor (TKI) selection in non-small cell lung cancer. Code 81210 describes BRAF gene analysis for V600 variants, also relevant in lung cancer but a different molecular target. Code 81275 describes KRAS variant analysis, used in colorectal and lung cancer but a different gene from EGFR. Code 81272 describes KIT gene analysis for variants in exons 9, 11, 13, and 17, associated with GIST — a different cancer type and gene. EGFR (81235) and BRAF (81210) are both routinely tested in NSCLC but represent distinct molecular targets with distinct CPT codes.

Question 2

A laboratory performs JAK2 p.Val617Phe (V617F) variant analysis on a patient with polycythemia vera. Which CPT® code is reported?

  1. 81270 (correct answer)
  2. 81275
  3. 81279
  4. 81271
Explanation: CPT® 81270 describes JAK2 (Janus kinase 2) gene analysis for the p.Val617Phe (V617F) variant — the correct code for the most common molecular test used to confirm a myeloproliferative neoplasm diagnosis, particularly polycythemia vera (>95%), essential thrombocythemia, and primary myelofibrosis. Code 81275 describes KRAS gene analysis for variants in codons 12 and 13, used in solid-organ cancers — not a myeloproliferative marker. Code 81279 describes JAK2 exon 12/13 sequence analysis, performed when JAK2 V617F is negative but polycythemia vera is still strongly suspected; V617F is the initial test ordered. Code 81271 describes HTT (huntingtin) gene analysis associated with Huntington disease — unrelated to myeloproliferative disorders.

Question 3

A laboratory performs HTT characterization of alleles including CAG repeat sizing for Huntington disease confirmation. Which CPT® code is reported?

  1. 81243
  2. 81244
  3. 81271 (correct answer)
  4. 81279
Explanation: CPT® 81271 describes HTT (huntingtin) gene analysis for characterization of alleles, including the expanded CAG trinucleotide repeat — the correct code for molecular confirmation of Huntington disease, which requires accurate repeat sizing to distinguish normal alleles (<36 CAG repeats), reduced penetrance alleles (36-39 repeats), and full penetrance alleles (40+ repeats). Code 81243 describes FMR1 gene analysis for detection of abnormal alleles in fragile X syndrome — also a trinucleotide repeat disorder but involving a different gene (CGG repeats in FMR1). Code 81244 describes FMR1 characterization of alleles including expanded allele size and methylation — again FMR1, not HTT. Code 81279 describes JAK2 exon 12/13 sequence analysis — a myeloproliferative neoplasm test unrelated to neurological trinucleotide repeat disorders.

Question 4

A laboratory performs targeted single-variant BRCA2 analysis for a known familial c.5946delT variant in a patient's first-degree relative. Which CPT® code is reported?

  1. 81217 (correct answer)
  2. 81216
  3. 81211
  4. 81213
Explanation: CPT® 81217 describes BRCA2 gene analysis for a known familial variant — the correct code for a targeted test that looks for one specific previously identified pathogenic mutation rather than sequencing the entire gene. This is a cost-effective cascade testing approach used after a proband's variant has been established. Code 81216 describes full BRCA2 gene sequence analysis, which is more comprehensive than necessary when the familial variant is already known. Code 81211 describes full sequence analysis of both BRCA1 and BRCA2 combined — also more comprehensive than necessary for targeted single-variant testing. Code 81213 describes BRCA1 and BRCA2 analysis for uncommon duplication/deletion variants; the known familial variant here is a single-nucleotide deletion, not a large rearrangement. Known familial variant testing (81215/81217) is always less expensive than full sequencing (81214/81216).

Question 5

A laboratory performs MTHFR common variant analysis (C677T and A1298C) as part of a thrombophilia workup. Which CPT® code is reported?

  1. 81241
  2. 81240
  3. 81291 (correct answer)
  4. 81256
Explanation: CPT® 81291 describes MTHFR (methylenetetrahydrofolate reductase) gene analysis for common variants — the correct code for testing the two most frequently analyzed MTHFR polymorphisms, C677T and A1298C, which affect folate metabolism and homocysteine levels. Code 81241 describes Factor V Leiden (F5) analysis — a distinct thrombophilia gene tested in the same clinical context but with its own CPT code. Code 81240 describes prothrombin F2 G20210A variant analysis — another thrombophilia gene frequently co-ordered with MTHFR but reported separately. Code 81256 describes HFE common variant analysis for hereditary hemochromatosis — unrelated to MTHFR or thrombophilia. In thrombophilia panels, 81241, 81240, and 81291 may all be ordered simultaneously but each requires its own CPT code.

Question 6

A laboratory performs KIT D816 variant analysis on a bone marrow specimen from a patient with suspected systemic mastocytosis. Which CPT® code is reported?

  1. 81272
  2. 81270
  3. 81275
  4. 81273 (correct answer)
Explanation: CPT® 81273 describes KIT gene analysis for the D816 variant — the correct code for targeted testing of the KIT D816V (and related D816 codon) substitution, present in more than 90% of systemic mastocytosis cases and the primary molecular confirmation test for this disorder. Code 81272 describes KIT analysis for variants in exons 9, 11, 13, and 17 — a broader panel used in GIST where multiple exons harbor activating mutations; the D816V variant in mastocytosis is specifically targeted by 81273. Code 81270 describes JAK2 V617F analysis for myeloproliferative neoplasms — not a KIT test. Code 81275 describes KRAS variant analysis for solid tumors — unrelated to mast cell disorders. The disease-specific D816 codon mutation in mastocytosis (81273) is distinct from the broader GIST KIT exon panel (81272).

Question 7

A molecular laboratory performs full MLH1 gene sequence analysis on a patient with a personal and family history of colorectal cancer for Lynch syndrome evaluation. Which CPT® code is reported?

  1. 81293
  2. 81288
  3. 81289
  4. 81292 (correct answer)
Explanation: CPT® 81292 describes MLH1 full gene sequence analysis — the correct code for comprehensive sequencing of the entire MLH1 coding region to identify germline pathogenic variants associated with Lynch syndrome when no prior familial mutation has been identified. Code 81293 describes MLH1 analysis for a known familial variant — a targeted test for a single specific mutation previously identified in a relative; no prior familial variant is specified here, requiring full sequencing. Code 81288 describes MLH1 promoter methylation analysis performed on tumor tissue to determine if MLH1 silencing is somatic; this is a germline blood evaluation, not a tumor methylation study. Code 81289 describes MLH1 duplication/deletion variant analysis for large intragenic rearrangements, typically an add-on to sequencing, not a standalone test.

Question 8

A laboratory performs CYP2C19 common variant analysis prior to initiating clopidogrel therapy following coronary stent placement. Which CPT® code is reported?

  1. 81226
  2. 81227
  3. 81225 (correct answer)
  4. 81230
Explanation: CPT® 81225 describes CYP2C19 (cytochrome P450, family 2, subfamily C, polypeptide 19) gene analysis for common variants — the correct code for pharmacogenomic testing of CYP2C19, responsible for activating clopidogrel (a prodrug) to its active metabolite. Poor metabolizers (loss-of-function alleles *2, *3) cannot adequately activate clopidogrel, increasing stent thrombosis risk; this test directly influences antiplatelet therapy selection. Code 81226 describes CYP2D6 common variant analysis, which predicts metabolism of opioids, antidepressants, and tamoxifen — a different enzyme unrelated to clopidogrel. Code 81227 describes CYP2C9 common variant analysis, relevant for warfarin and NSAID metabolism — different from CYP2C19 despite similar nomenclature. Code 81230 describes CYP3A4 analysis. CYP2C19 (81225) is specifically indicated for clopidogrel pharmacogenomics; CYP2C9 (81227) is specifically indicated for warfarin pharmacogenomics.

Question 9

A laboratory performs CFTR intron 8 poly-T repeat analysis (5T/7T/9T) as a reflex test after a common variant panel returned a single heterozygous variant. Which CPT® code is reported?

  1. 81224 (correct answer)
  2. 81220
  3. 81223
  4. 81221
Explanation: CPT® 81224 describes CFTR gene analysis for the intron 8 poly-T repeat (5T, 7T, and 9T alleles) — the correct code for targeted analysis of the thymidine stretch in CFTR intron 8, where the 5T allele reduces exon 9 splicing efficiency and is associated with CBAVD and mild CFTR-related disorders. Code 81220 describes CFTR common variant panel testing (the 23-variant or equivalent panel), which is typically ordered first and was the preceding test; poly-T analysis is an additional or reflex test. Code 81223 describes full CFTR gene sequence analysis; poly-T analysis is a targeted repeat/splice analysis distinct from full sequencing. Code 81221 describes CFTR analysis for a known familial variant; no prior familial variant is the basis for this test. Intron 8 poly-T analysis (81224) is a specialized CFTR test distinct from standard variant panels and full gene sequencing.

Question 10

A clinical laboratory performs whole exome sequencing on a pediatric patient with a complex undiagnosed syndrome after targeted gene panels yielded no diagnosis. Which CPT® code is reported?

  1. 81445
  2. 81450
  3. 81455
  4. 81415 (correct answer)
Explanation: CPT® 81415 describes exome (whole exome) sequencing, germline — the correct code for diagnostic sequencing of the entire protein-coding exome to identify pathogenic variants in a constitutional (germline) context, such as a child with a complex undiagnosed syndrome. Code 81460 describes whole genome sequencing (not exome), which sequences both coding and non-coding regions and is a more extensive and distinct procedure from whole exome sequencing. Code 81445 describes a targeted genomic sequence analysis panel for solid organ neoplasm (5-50 genes); this is a germline undiagnosed condition in a child, not a solid tumor. Code 81450 describes a hematolymphoid neoplasm targeted panel; this patient does not have a hematologic malignancy. Code 81455 describes a targeted panel exceeding 50 genes for oncology use. Whole exome sequencing (81415) is distinguished from targeted panels by the breadth of genomic coverage — all protein-coding regions rather than a predefined subset — and from whole genome sequencing (81460) by analyzing only the exonic portion.

Question 11

A laboratory performs BRAF V600 variant analysis on a melanoma specimen to guide BRAF inhibitor therapy. Which CPT® code is reported?

  1. 81210 (correct answer)
  2. 81275
  3. 81235
  4. 81272
Explanation: CPT® 81210 describes BRAF (v-raf murine sarcoma viral oncogene homolog B1) gene analysis for V600 variants — the correct code for testing BRAF for the V600E and other V600 substitutions that predict response to vemurafenib, dabrafenib, and other BRAF inhibitors in metastatic melanoma. Code 81275 describes KRAS variant analysis; KRAS is not the gene analyzed here. Code 81235 describes EGFR common variant analysis, relevant in lung cancer; EGFR testing is not the standard for melanoma targeted therapy. Code 81272 describes KIT gene analysis for variants in exons 9, 11, 13, and 17, associated with GIST and certain melanoma subtypes, but the V600 BRAF variant is the primary molecular target here. BRAF V600 mutations are present in approximately 50% of cutaneous melanomas and are specifically captured by 81210.

Question 12

A laboratory performs comprehensive sequencing of the entire BRCA1 coding region to identify any pathogenic variant in a patient with no known familial mutation. Which CPT® code is reported?

  1. 81212
  2. 81215
  3. 81217
  4. 81214 (correct answer)
Explanation: CPT® 81214 describes BRCA1 gene analysis with full gene sequence — the correct code when comprehensive sequencing of the entire BRCA1 coding region is performed to identify any pathogenic variant when no known familial mutation exists. Code 81212 describes analysis of three specific founder variants in BRCA1 and BRCA2 associated with Ashkenazi Jewish ancestry — a targeted panel, not comprehensive sequence analysis. Code 81215 describes BRCA1 analysis for a known familial variant — a targeted test for a single specific mutation already identified in a family member; no prior familial mutation is known here, requiring full sequencing. Code 81217 describes BRCA2 analysis for a known familial variant; this code applies to BRCA2, not BRCA1. Full sequence analysis (81214) detects any pathogenic variant in BRCA1 without prior knowledge of the mutation.

Question 13

A hematology laboratory performs Factor V Leiden variant analysis on a patient with unprovoked venous thromboembolism. Which CPT® code is reported?

  1. 81241 (correct answer)
  2. 81240
  3. 81291
  4. 81243
Explanation: CPT® 81241 describes F5 (coagulation factor V) gene analysis for the Leiden variant (c.1691G>A, p.Arg534Gln) — the correct code for the most common inherited thrombophilia mutation tested in patients with unexplained venous thromboembolism. Code 81240 describes F2 (prothrombin) gene analysis for the G20210A variant — a different thrombophilia gene; both F5 and F2 are commonly tested together but have distinct CPT codes. Code 81291 describes MTHFR gene analysis for common variants (C677T and A1298C); MTHFR is also included in thrombophilia evaluations but represents a different gene. Code 81243 describes FMR1 gene analysis for detection of abnormal alleles associated with fragile X syndrome — unrelated to thrombophilia. Factor V Leiden (81241) and prothrombin G20210A (81240) are frequently ordered together but are reported with separate CPT codes.

Question 14

A laboratory performs a targeted BRCA1/BRCA2 three-variant panel for the Ashkenazi Jewish founder mutations (185delAG, 5385insC, and 6174delT) on a patient of Ashkenazi Jewish ancestry. Which CPT® code is reported?

  1. 81211
  2. 81212 (correct answer)
  3. 81214
  4. 81216
Explanation: CPT® 81212 describes BRCA1 and BRCA2 analysis for the three specific Ashkenazi Jewish founder mutations (185delAG and 5385insC in BRCA1; 6174delT in BRCA2) — the correct code for the targeted panel used in individuals of Ashkenazi Jewish ancestry, where these three variants account for the vast majority of BRCA-related hereditary cancer risk in that population. Code 81211 describes full gene sequence analysis of both BRCA1 and BRCA2 combined — comprehensive evaluation not limited to three variants. Code 81214 describes full sequence analysis of BRCA1 only. Code 81216 describes full sequence analysis of BRCA2 only. The three-founder-variant Ashkenazi panel (81212) is a less expensive initial screening option for Ashkenazi Jewish patients; full sequencing is reserved when the targeted panel is negative or when non-Ashkenazi-specific risk is present.

Question 15

A pathology laboratory performs KRAS codon 12/13 variant analysis on a colorectal cancer specimen to guide anti-EGFR antibody therapy selection. Which CPT® code is reported?

  1. 81210
  2. 81275 (correct answer)
  3. 81235
  4. 81276
Explanation: CPT® 81275 describes KRAS gene analysis for variants in codons 12 and 13 — the correct code for KRAS testing performed to guide anti-EGFR antibody therapy selection in colorectal cancer. KRAS mutations at codons 12 and 13 predict resistance to cetuximab and panitumumab. Code 81210 describes BRAF gene analysis for V600 variants, also used in colorectal and other cancers but targeting a different gene. Code 81235 describes EGFR gene analysis for common variants, used primarily in non-small cell lung cancer; EGFR variants predict response to TKIs, not anti-EGFR antibody therapy in colorectal cancer. Code 81276 describes KRAS analysis for additional variants beyond codons 12 and 13 (e.g., codons 59, 61, 117, 146); the initial codon 12/13 panel is reported with 81275.

Question 16

A laboratory performs a CFTR common variant carrier screening panel (23-variant) on a reproductive-age patient with no prior family history. Which CPT® code is reported?

  1. 81223
  2. 81221
  3. 81222
  4. 81220 (correct answer)
Explanation: CPT® 81220 describes CFTR gene analysis for common variants — the correct code for the standard carrier screening panel testing a defined set of common pathogenic CFTR variants (typically the ACMG-recommended 23-variant panel). Code 81223 describes full CFTR gene sequence analysis, which detects rare and uncommon variants beyond the standard panel; carrier screening in a low-risk individual uses the common variant panel (81220), not full sequencing. Code 81221 describes analysis for a known familial CFTR variant — a targeted test performed when a specific pathogenic variant has already been identified in a family member; no prior familial variant is referenced here. Code 81222 describes CFTR analysis for duplication/deletion variants, which detects large rearrangements; this is typically an add-on to sequencing, not a standalone carrier screening test.

Question 17

A clinical laboratory performs BCR/ABL1 major breakpoint (p210) quantitative PCR for CML treatment monitoring. Which CPT® code is reported?

  1. 81207
  2. 81206 (correct answer)
  3. 81208
  4. 81275
Explanation: CPT® 81206 describes BCR/ABL1 (t(9;22)) translocation analysis for the major breakpoint (p210), quantitative — the correct code for quantitative PCR measurement of the BCR/ABL1 p210 fusion transcript, the predominant transcript in CML, used for diagnosis, treatment monitoring, and assessment of major molecular response. Code 81207 describes BCR/ABL1 analysis for the minor breakpoint (p190), associated with B-cell ALL, not CML. Code 81208 describes BCR/ABL1 analysis for other specified breakpoints (e.g., p230 in chronic neutrophilic leukemia). Code 81275 describes KRAS variant analysis, which is used in solid tumors, not CML monitoring. The major (p210) vs. minor (p190) breakpoint distinction between 81206 and 81207 corresponds to the clinical distinction between CML and ALL, respectively.

Question 18

A laboratory performs FMR1 characterization including expanded allele size and methylation status on a male patient with suspected fragile X syndrome. Which CPT® code is reported?

  1. 81244 (correct answer)
  2. 81271
  3. 81253
  4. 81243
Explanation: CPT® 81244 describes FMR1 (fragile X mental retardation 1) gene analysis for characterization of alleles (expanded allele characterization) — the correct code when the analysis includes both expanded allele size determination and methylation status assessment, which together distinguish full mutations from premutations and characterize allele subtypes in detail. Code 81243 describes FMR1 gene analysis for detection of abnormal alleles only — a less comprehensive test that identifies the presence of an abnormal (expanded) allele but does not include full characterization of expanded size and methylation; when the stem specifically describes both size and methylation characterization, 81244 is required over 81243. Code 81271 describes HTT (huntingtin) gene analysis for characterization of alleles associated with Huntington disease — also a trinucleotide repeat disorder but involving a different gene (CAG repeats in HTT). Code 81253 describes GJB2 (connexin 26) gene analysis for a known familial variant associated with hereditary hearing loss, unrelated to fragile X.

Question 19

A laboratory performs CYP2D6 common variant analysis for pharmacogenomic profiling prior to initiating tamoxifen therapy. Which CPT® code is reported?

  1. 81225
  2. 81227
  3. 81230
  4. 81226 (correct answer)
Explanation: CPT® 81226 describes CYP2D6 (cytochrome P450 2D6) gene analysis for common variants — the correct code for pharmacogenomic testing to predict an individual's capacity to metabolize drugs that are CYP2D6 substrates, including codeine, tricyclic antidepressants, antipsychotics, and tamoxifen. CYP2D6 metabolizer status (poor, intermediate, normal/extensive, ultra-rapid) is critical for dosing and toxicity avoidance. Code 81225 describes CYP2C19 analysis, which predicts metabolism of clopidogrel, proton pump inhibitors, and certain antidepressants — a different enzyme. Code 81227 describes CYP2C9 analysis, which predicts warfarin and NSAIDs metabolism. Code 81230 describes CYP3A4 analysis. Each cytochrome P450 enzyme has its own pharmacogenomics code; CYP2D6 is specifically reported with 81226.

Question 20

A laboratory performs FLT3 internal tandem duplication (ITD) variant analysis on an AML patient at diagnosis. Which CPT® code is reported?

  1. 81246
  2. 81245 (correct answer)
  3. 81270
  4. 81275
Explanation: CPT® 81245 describes FLT3 (FMS-like tyrosine kinase 3) gene analysis for internal tandem duplication (ITD) variants — the correct code for detection of FLT3-ITD mutations in approximately 25-30% of AML cases, conferring adverse prognosis and guiding FLT3 inhibitor therapy. Code 81246 describes FLT3 analysis for tyrosine kinase domain (TKD) variants (e.g., D835 point mutations), a distinct class of FLT3 mutations; both ITD and TKD are commonly co-ordered but reported separately. Code 81270 describes JAK2 V617F analysis for myeloproliferative neoplasms, not AML. Code 81275 describes KRAS variant analysis, relevant in solid tumors and some hematologic malignancies but not the primary FLT3 test. The ITD (81245) versus TKD (81246) distinction reflects different mutation types within the same FLT3 gene.