I85PREP
⌘ K
ABPath Molecular Genetic Pathology study materials
ABPath Molecular Genetic Pathology study resources

ABPath Molecular Genetic Pathology practice questions

One question at a time. Build your ABPath Molecular Genetic Pathology understanding.

First 50 of 200 questions. Each one lists the choices, the correct answer, and an explanation. The checker at the top of this page saves progress in this browser when it is available.

Continue in the practice tool above to load more questions, 50 at a time.

Question 1Normal structure/function, molecular techniques/methods, human genetic principles including DNA/RNA structure, transcription/translation, types of mutation and their detection, mutation nomenclature, gene structure and function, population and risk calculation

Which enzyme catalyzes the addition of deoxynucleotide triphosphates to a growing DNA strand during replication?

  1. DNA ligase
  2. RNA polymerase
  3. Helicase
  4. DNA polymerase Correct answer.

Explanation

DNA polymerases add dNTPs to the 3'-OH end of a primer strand, extending it in a template-directed manner. Ligase joins pre-existing strand breaks, polymerase transcribes RNA, and helicase unwinds duplex DNA.

Question 2Normal structure/function, molecular techniques/methods, human genetic principles including DNA/RNA structure, transcription/translation, types of mutation and their detection, mutation nomenclature, gene structure and function, population and risk calculation

During transcription, which strand of a gene serves as the template for RNA synthesis?

  1. The strand determined by the promoter orientation
  2. The antisense (noncoding) strand Correct answer.
  3. Both strands simultaneously
  4. The coding (sense) strand

Explanation

RNA polymerase reads the antisense (template) strand in the 3'-to-5' direction, producing an RNA identical in sequence to the coding strand (with U replacing T). The coding strand is not read by the polymerase.

Question 3Normal structure/function, molecular techniques/methods, human genetic principles including DNA/RNA structure, transcription/translation, types of mutation and their detection, mutation nomenclature, gene structure and function, population and risk calculation

A single base substitution changes a codon from UAC to UAA. What is the consequence for the encoded protein?

  1. A missense substitution
  2. A silent mutation
  3. A nonsense (stop) mutation Correct answer.
  4. A frameshift mutation

Explanation

UAA is a stop codon, so the substitution introduces premature termination, which is a nonsense mutation. Silent changes do not alter the amino acid, missense changes one amino acid, and frameshifts arise from insertions or deletions not divisible by three.

Question 4Normal structure/function, molecular techniques/methods, human genetic principles including DNA/RNA structure, transcription/translation, types of mutation and their detection, mutation nomenclature, gene structure and function, population and risk calculation

Which nomenclature correctly describes a substitution of adenine for guanine at coding nucleotide position 1234?

  1. c.1234delG
  2. c.1234_1235insA
  3. c.1234G>A Correct answer.
  4. c.1234A>G

Explanation

HGVS nomenclature writes the reference nucleotide first, followed by the observed nucleotide, so a change from G to A is c.1234G>A. The other options describe different variant types or reverse the reference and observed bases.

Question 5Normal structure/function, molecular techniques/methods, human genetic principles including DNA/RNA structure, transcription/translation, types of mutation and their detection, mutation nomenclature, gene structure and function, population and risk calculation

In a population at Hardy-Weinberg equilibrium, the frequency of a recessive disease allele is 0.1. What proportion of the population is expected to be heterozygous carriers?

  1. 0.09
  2. 0.81
  3. 0.18 Correct answer.
  4. 0.01

Explanation

With q = 0.1, p = 0.9, and the carrier frequency 2pq = 2(0.9)(0.1) = 0.18. The homozygous affected frequency is q² = 0.01 and the homozygous unaffected frequency is p² = 0.81.

Question 6Normal structure/function, molecular techniques/methods, human genetic principles including DNA/RNA structure, transcription/translation, types of mutation and their detection, mutation nomenclature, gene structure and function, population and risk calculation

Which feature distinguishes eukaryotic mRNA from prokaryotic mRNA?

  1. Use of uracil in place of thymine
  2. Presence of a Shine-Dalgarno sequence
  3. Translation coupled to transcription
  4. Presence of a 5' cap and poly(A) tail Correct answer.

Explanation

Eukaryotic mRNAs are processed with a 5' 7-methylguanosine cap and a 3' poly(A) tail, which are absent from typical prokaryotic messages. Uracil is used in all RNA, and coupled transcription-translation and Shine-Dalgarno sequences are prokaryotic features.

Question 7Normal structure/function, molecular techniques/methods, human genetic principles including DNA/RNA structure, transcription/translation, types of mutation and their detection, mutation nomenclature, gene structure and function, population and risk calculation

Which type of mutation most commonly results from slipped-strand mispairing during replication of a short tandem repeat?

  1. Chromosomal translocation
  2. Change in repeat copy number Correct answer.
  3. Inversion
  4. Point substitution

Explanation

Slipped-strand mispairing during replication causes expansion or contraction in the number of repeat units, producing length polymorphisms. Substitutions, translocations, and inversions arise through different mechanisms.

Question 8Normal structure/function, molecular techniques/methods, human genetic principles including DNA/RNA structure, transcription/translation, types of mutation and their detection, mutation nomenclature, gene structure and function, population and risk calculation

A PCR reaction fails to amplify a product despite intact template. Which step is most directly dependent on the primer's melting temperature?

  1. Denaturation
  2. Annealing Correct answer.
  3. Extension
  4. Final hold

Explanation

The annealing step depends on primers hybridizing to complementary sequences, and the annealing temperature is set relative to primer melting temperature. Denaturation depends on double-strand melting, extension on polymerase activity, and the final hold is for storage.

Question 9Normal structure/function, molecular techniques/methods, human genetic principles including DNA/RNA structure, transcription/translation, types of mutation and their detection, mutation nomenclature, gene structure and function, population and risk calculation

Sanger sequencing relies on which property of dideoxynucleotides?

  1. They lack a 3'-hydroxyl group and terminate chain elongation Correct answer.
  2. They prevent template denaturation
  3. They fluoresce when incorporated
  4. They are incorporated more rapidly than dNTPs

Explanation

Dideoxynucleotides lack the 3'-OH needed for the next phosphodiester bond, so incorporation terminates the growing chain and generates a ladder of fragments. Fluorescence comes from labels attached to the terminators, not an intrinsic property.

Question 10Normal structure/function, molecular techniques/methods, human genetic principles including DNA/RNA structure, transcription/translation, types of mutation and their detection, mutation nomenclature, gene structure and function, population and risk calculation

A patient is heterozygous for a deletion of four nucleotides in a coding exon. What is the expected effect on the reading frame?

  1. No effect on the reading frame
  2. A shift in the reading frame downstream of the deletion Correct answer.
  3. Deletion of exactly one amino acid
  4. A silent substitution

Explanation

Deletions not divisible by three shift the reading frame, altering all downstream codons and usually producing premature termination. Deletions of three nucleotides remove one amino acid without shifting the frame.

Question 11Normal structure/function, molecular techniques/methods, human genetic principles including DNA/RNA structure, transcription/translation, types of mutation and their detection, mutation nomenclature, gene structure and function, population and risk calculation

Which component of the spliceosome recognizes the branch point adenosine during intron removal?

  1. The poly(A) polymerase
  2. U1 snRNP
  3. U6 snRNP
  4. U2 snRNP Correct answer.

Explanation

U2 snRNP base-pairs with the branch point sequence and positions the branch adenosine for the first transesterification. U1 recognizes the 5' splice site, U6 participates in catalysis, and poly(A) polymerase functions in 3' end processing.

Question 12Normal structure/function, molecular techniques/methods, human genetic principles including DNA/RNA structure, transcription/translation, types of mutation and their detection, mutation nomenclature, gene structure and function, population and risk calculation

Which genetic principle states that alleles of different genes assort independently when located on different chromosomes?

  1. Pleiotropy
  2. Independent assortment Correct answer.
  3. Linkage
  4. Segregation

Explanation

Mendel's law of independent assortment describes random distribution of alleles for genes on different chromosomes. Segregation concerns the two alleles of a single gene, linkage concerns genes on the same chromosome, and pleiotropy is one gene affecting multiple traits.

Question 13Normal structure/function, molecular techniques/methods, human genetic principles including DNA/RNA structure, transcription/translation, types of mutation and their detection, mutation nomenclature, gene structure and function, population and risk calculation

Two carrier parents (both heterozygous for an autosomal recessive allele) have a child. What is the probability the child is a carrier, given that the child is unaffected?

  1. 2/3 Correct answer.
  2. 1/4
  3. 1/2
  4. 3/4

Explanation

Among unaffected offspring of two carriers, the genotypes are AA or Aa in a 1:2 ratio, so the probability of being a carrier conditional on unaffected status is 2/3. The unconditional carrier probability is 1/2.

Question 14Normal structure/function, molecular techniques/methods, human genetic principles including DNA/RNA structure, transcription/translation, types of mutation and their detection, mutation nomenclature, gene structure and function, population and risk calculation

Which type of RNA carries amino acids to the ribosome during translation?

  1. snRNA
  2. tRNA Correct answer.
  3. rRNA
  4. mRNA

Explanation

Transfer RNA (tRNA) is charged with amino acids and delivers them to the ribosome by matching its anticodon to the mRNA codon. mRNA is the template, rRNA forms the ribosome, and snRNA functions in splicing.

Question 15Normal structure/function, molecular techniques/methods, human genetic principles including DNA/RNA structure, transcription/translation, types of mutation and their detection, mutation nomenclature, gene structure and function, population and risk calculation

A variant is described as p.Arg273His. What does this nomenclature indicate?

  1. Arginine at position 273 is replaced by histidine Correct answer.
  2. A deletion of arginine at position 273
  3. Histidine at position 273 is replaced by arginine
  4. A frameshift beginning at codon 273

Explanation

Protein-level HGVS nomenclature writes the reference amino acid first, then the position, then the substituted amino acid, so p.Arg273His means arginine changes to histidine. Deletions and frameshifts use different designators.

Question 16Normal structure/function, molecular techniques/methods, human genetic principles including DNA/RNA structure, transcription/translation, types of mutation and their detection, mutation nomenclature, gene structure and function, population and risk calculation

Which feature of the genetic code allows a single amino acid to be specified by more than one codon?

  1. Universality
  2. Degeneracy Correct answer.
  3. Commaless reading
  4. Non-overlapping reading

Explanation

Degeneracy refers to the redundancy of the code, where multiple codons specify the same amino acid, typically differing at the third position. Universality means the same code is used across organisms, and non-overlapping/commaless describe how codons are read.

Question 17Normal structure/function, molecular techniques/methods, human genetic principles including DNA/RNA structure, transcription/translation, types of mutation and their detection, mutation nomenclature, gene structure and function, population and risk calculation

In a family, a disease allele shows complete penetrance and is inherited in an autosomal dominant pattern. An affected heterozygous parent has an unaffected partner. What is the probability that a given child is affected?

  1. 3/4
  2. 0
  3. 1/4
  4. 1/2 Correct answer.

Explanation

A heterozygous affected parent transmits the disease allele to half of gametes, so each child has a 1/2 chance of inheriting the dominant allele and being affected. The unaffected partner contributes only normal alleles.

Question 18Normal structure/function, molecular techniques/methods, human genetic principles including DNA/RNA structure, transcription/translation, types of mutation and their detection, mutation nomenclature, gene structure and function, population and risk calculation

Which technique detects a specific DNA sequence by hybridization of a labeled probe to a membrane-bound sample?

  1. Southern blot Correct answer.
  2. ELISA
  3. Northern blot
  4. Western blot

Explanation

Southern blotting separates DNA by electrophoresis, transfers it to a membrane, and detects specific fragments by probe hybridization. Western blot detects protein, Northern blot detects RNA, and ELISA detects antigen-antibody interactions.

Question 19Normal structure/function, molecular techniques/methods, human genetic principles including DNA/RNA structure, transcription/translation, types of mutation and their detection, mutation nomenclature, gene structure and function, population and risk calculation

A quantitative PCR assay reports a higher Ct value for a sample than for a calibrator. How should this be interpreted?

  1. The sample contains inhibitors
  2. The assay failed and the result is invalid
  3. The target is more abundant in the sample
  4. The target is less abundant in the sample Correct answer.

Explanation

Ct is inversely related to starting template amount: a higher Ct indicates fewer target copies, requiring more amplification cycles to cross threshold. Inhibitors would typically suppress amplification of controls as well, and validity depends on control results.

Question 20Normal structure/function, molecular techniques/methods, human genetic principles including DNA/RNA structure, transcription/translation, types of mutation and their detection, mutation nomenclature, gene structure and function, population and risk calculation

Which DNA repair pathway corrects bulky, helix-distorting lesions such as ultraviolet-induced pyrimidine dimers?

  1. Mismatch repair
  2. Nucleotide excision repair Correct answer.
  3. Nonhomologous end joining
  4. Base excision repair

Explanation

Nucleotide excision repair removes a short oligonucleotide segment containing bulky adducts and dimers. Mismatch repair corrects replication errors, base excision repair handles small base lesions, and nonhomologous end joining repairs double-strand breaks.

Question 21Normal structure/function, molecular techniques/methods, human genetic principles including DNA/RNA structure, transcription/translation, types of mutation and their detection, mutation nomenclature, gene structure and function, population and risk calculation

Which statement about the structure of the DNA double helix is correct?

  1. The two strands are parallel with A pairing to G
  2. Base pairs are held together by phosphodiester bonds
  3. Purines pair with purines across the helix
  4. The two strands are antiparallel with A pairing to T and G pairing to C Correct answer.

Explanation

The DNA duplex consists of antiparallel strands with complementary Watson-Crick pairing of adenine to thymine and guanine to cytosine, held by hydrogen bonds. Phosphodiester bonds form the sugar-phosphate backbone, not the base pairing.

Question 22Normal structure/function, molecular techniques/methods, human genetic principles including DNA/RNA structure, transcription/translation, types of mutation and their detection, mutation nomenclature, gene structure and function, population and risk calculation

A synonymous (silent) variant occurs at the last nucleotide of an exon. Which mechanism could still make it pathogenic?

  1. It alters the amino acid sequence directly
  2. It causes a frameshift
  3. It creates a stop codon
  4. It disrupts normal splicing Correct answer.

Explanation

Exonic variants near splice junctions can disrupt splice donor or acceptor recognition, causing exon skipping or cryptic splice use even though the codon change is synonymous. Silent variants do not directly alter the amino acid, shift the frame, or create a stop codon.

Question 23Normal structure/function, molecular techniques/methods, human genetic principles including DNA/RNA structure, transcription/translation, types of mutation and their detection, mutation nomenclature, gene structure and function, population and risk calculation

Which property of the genetic code explains why a single base substitution can be harmless?

  1. The code is universal, so substitutions are always silent
  2. The code contains no stop codons
  3. The code is degenerate, so third-position changes often do not alter the amino acid Correct answer.
  4. The code is overlapping, so most substitutions are corrected

Explanation

Degeneracy, especially at the third codon position, means many substitutions produce the same amino acid (synonymous changes). Overlapping and universality do not confer harmlessness, and the code does contain stop codons.

Question 24Normal structure/function, molecular techniques/methods, human genetic principles including DNA/RNA structure, transcription/translation, types of mutation and their detection, mutation nomenclature, gene structure and function, population and risk calculation

Which molecule serves as the primer for DNA polymerase during eukaryotic chromosomal replication?

  1. A poly(A) tail
  2. A short DNA primer synthesized by ligase
  3. A short RNA primer synthesized by primase Correct answer.
  4. A protein primer

Explanation

Primase synthesizes a short RNA primer that provides a 3'-OH for DNA polymerase to extend. Ligase does not synthesize primers, and poly(A) tails are added to mRNA, not used in replication.

Question 25Normal structure/function, molecular techniques/methods, human genetic principles including DNA/RNA structure, transcription/translation, types of mutation and their detection, mutation nomenclature, gene structure and function, population and risk calculation

A laboratory performs allele-specific PCR to detect a known point mutation. Which design element is essential for specificity?

  1. A long extension time
  2. A high-fidelity proofreading polymerase
  3. A primer with a fluorescent label at the 5' end
  4. A primer whose 3' end matches the variant base Correct answer.

Explanation

Allele-specific PCR relies on a primer whose 3' terminal base is complementary to the variant, so extension occurs only when the match is perfect. Labeling, proofreading activity, and extension time do not confer allele discrimination.

Question 26Quality improvement, quality control, quality assurance and ethical, legal, and regulatory issues relating to molecular genetic laboratory testing

Which federal statute establishes the basic privacy protections for individually identifiable health information held by most clinical laboratories in the United States?

  1. The Clinical Laboratory Improvement Amendments
  2. The Federal Food, Drug, and Cosmetic Act
  3. The Genetic Information Nondiscrimination Act
  4. The Health Insurance Portability and Accountability Act Correct answer.

Explanation

HIPAA, through its Privacy and Security Rules, governs the use and disclosure of protected health information by covered entities, which include most clinical laboratories. CLIA addresses laboratory quality standards rather than privacy of health information.

Question 27Quality improvement, quality control, quality assurance and ethical, legal, and regulatory issues relating to molecular genetic laboratory testing

Under CLIA, a laboratory that performs high-complexity molecular testing must hold which type of certificate?

  1. A research-use-only registration
  2. A certificate for provider-performed microscopy
  3. A certificate of waiver
  4. A certificate of compliance or accreditation Correct answer.

Explanation

High-complexity testing requires a CLIA certificate of compliance or a certificate of accreditation through an approved accrediting organization. Waived and provider-performed microscopy certificates cover only limited, simpler testing categories.

Question 28Quality improvement, quality control, quality assurance and ethical, legal, and regulatory issues relating to molecular genetic laboratory testing

A laboratory validates a new next-generation sequencing panel. Which element is required for the validation to meet professional molecular pathology standards?

  1. Establishing accuracy, precision, analytical sensitivity, and specificity before reporting patient results Correct answer.
  2. Reporting results under a research-use-only disclaimer until publications are available
  3. Deferring validation until the first ten clinical specimens have been reported
  4. Confirming only that the reference laboratory uses the same instrument model

Explanation

Method validation for a laboratory-developed test must establish performance characteristics including accuracy, precision, analytical sensitivity, analytical specificity, reportable range, and reference intervals before clinical use. Reporting before validation or relying solely on instrument matching does not satisfy these requirements.

Question 29Quality improvement, quality control, quality assurance and ethical, legal, and regulatory issues relating to molecular genetic laboratory testing

Which action best describes an appropriate response when a laboratory identifies a clerical error that caused a wrong patient's genotype to be reported?

  1. Delete the original report from the laboratory information system
  2. Issue an amended report, document the event, and evaluate whether the error affected clinical care Correct answer.
  3. Silently correct the record and take no further action
  4. Wait for the next scheduled inspection to disclose the error

Explanation

Errors affecting reported results require an amended or corrected report, documentation through the quality management system, and assessment of clinical impact as part of incident review. Concealment, deletion, or delayed disclosure undermines quality assurance and regulatory compliance.

Question 30Quality improvement, quality control, quality assurance and ethical, legal, and regulatory issues relating to molecular genetic laboratory testing

A laboratory uses a commercially distributed companion diagnostic assay. Which statement best describes the regulatory status of modifying the assay's specimen type beyond its labeled claims?

  1. No validation is needed if the nucleic acid extraction method is unchanged
  2. The modification is automatically covered by the manufacturer's clearance
  3. The modification requires only a verbal approval from the laboratory director
  4. The laboratory assumes responsibility for validating the new specimen type as a laboratory-developed test Correct answer.

Explanation

When a laboratory modifies a cleared or approved test beyond its labeled intended use, the laboratory generally assumes responsibility for establishing performance, effectively functioning as a laboratory-developed test. The manufacturer's clearance does not extend to off-label modifications.

Question 31Quality improvement, quality control, quality assurance and ethical, legal, and regulatory issues relating to molecular genetic laboratory testing

Which entity is responsible for maintaining the proficiency testing requirement for laboratories performing molecular genetic testing under CLIA?

  1. The hospital's risk management office
  2. The Centers for Medicare & Medicaid Services through approved proficiency testing programs Correct answer.
  3. The laboratory's institutional review board
  4. The assay manufacturer's quality department

Explanation

CMS administers CLIA and requires laboratories to enroll in approved proficiency testing programs for regulated analytes, with oversight through approved providers. Institutional review boards, manufacturers, and risk management do not set proficiency testing requirements.

Question 32Quality improvement, quality control, quality assurance and ethical, legal, and regulatory issues relating to molecular genetic laboratory testing

A patient asks that a previously reported germline variant result be removed from the medical record because family members might learn of it. What is the most appropriate laboratory response?

  1. Forward the request to the employer's human resources department
  2. Explain that results are retained per recordkeeping requirements and discuss privacy protections Correct answer.
  3. Amend the report to remove the variant but keep a private note
  4. Delete the result from the record as requested

Explanation

Laboratory records must be retained according to regulatory and accreditation requirements, and results generally cannot be deleted on patient request. The appropriate response is to explain retention obligations and applicable privacy protections.

Question 33Quality improvement, quality control, quality assurance and ethical, legal, and regulatory issues relating to molecular genetic laboratory testing

Which of the following is the primary purpose of a laboratory's quality control program for molecular assays?

  1. To increase test throughput
  2. To replace the need for proficiency testing
  3. To detect analytical errors and ensure results meet defined performance specifications Correct answer.
  4. To satisfy marketing requirements of assay manufacturers

Explanation

Quality control monitors assay performance to detect analytical errors and confirm that results conform to defined specifications. QC does not replace proficiency testing and is not intended to boost throughput or serve marketing aims.

Question 34Quality improvement, quality control, quality assurance and ethical, legal, and regulatory issues relating to molecular genetic laboratory testing

A laboratory reports a somatic variant using a nomenclature standard. Which practice best supports accurate and unambiguous reporting?

  1. Using a consistent, recognized variant nomenclature with transcript and genome build specified Correct answer.
  2. Reporting only the protein change without the nucleotide change
  3. Describing variants in free text unique to each technologist
  4. Omitting the reference transcript to save space

Explanation

Accurate reporting requires a recognized nomenclature system with the reference transcript and genome build specified so that variants can be interpreted unambiguously. Incomplete or free-text descriptions invite misinterpretation.

Question 35Quality improvement, quality control, quality assurance and ethical, legal, and regulatory issues relating to molecular genetic laboratory testing

A laboratory discovers that its reference range for a molecular assay was erroneously transcribed. Which quality activity is most directly triggered?

  1. An institutional review board submission
  2. A corrective and preventive action review Correct answer.
  3. A change in the laboratory's CLIA certificate category
  4. A new proficiency testing enrollment

Explanation

An identified error in reported reference information should prompt a corrective and preventive action process to correct the issue, assess impact, and prevent recurrence. It does not change the CLIA certificate category or require IRB review.

Question 36Quality improvement, quality control, quality assurance and ethical, legal, and regulatory issues relating to molecular genetic laboratory testing

Which of the following best describes the role of the laboratory director in a CLIA-certified molecular laboratory?

  1. Performing only administrative billing functions
  2. Reviewing results only when a clinician requests it
  3. Ensuring overall quality, approving procedures, and assuring compliance with applicable regulations Correct answer.
  4. Delegating all quality oversight to the technical supervisor without review

Explanation

The laboratory director is ultimately responsible for the overall operation and quality of the laboratory, including approving procedures and ensuring regulatory compliance. This responsibility cannot be fully delegated away.

Question 37Quality improvement, quality control, quality assurance and ethical, legal, and regulatory issues relating to molecular genetic laboratory testing

A laboratory wants to use residual clinical specimens for assay development. Which consideration is most relevant to ethical and regulatory compliance?

  1. Specimens may be used freely with no review because they are residual
  2. Specimens must be destroyed rather than used for any secondary purpose
  3. Consent is never relevant for any residual specimen use
  4. Use should follow institutional policy on de-identification and, where applicable, human subjects review Correct answer.

Explanation

Secondary use of residual specimens must comply with institutional policies and, depending on de-identification and intent, may require human subjects review or consent. Residual status alone does not eliminate these obligations.

Question 38Quality improvement, quality control, quality assurance and ethical, legal, and regulatory issues relating to molecular genetic laboratory testing

Which document typically defines the laboratory's written policies for specimen handling, test performance, and quality assessment in a molecular laboratory?

  1. The standard operating procedures manual Correct answer.
  2. The hospital discharge summary template
  3. The assay's research publication
  4. The manufacturer's package insert only

Explanation

Standard operating procedures document the laboratory's approved policies and instructions for specimen handling, testing, and quality assessment. Package inserts, discharge templates, and publications do not substitute for the laboratory's own procedures.

Question 39Quality improvement, quality control, quality assurance and ethical, legal, and regulatory issues relating to molecular genetic laboratory testing

A laboratory receives a proficiency testing specimen for a molecular assay and the result falls outside the acceptable range. What is the most appropriate initial action?

  1. Immediately report the result as the patient result
  2. Investigate the discrepancy, document findings, and implement corrective action as needed Correct answer.
  3. Discard the proficiency testing record
  4. Repeat testing until a passing result is obtained and report only that

Explanation

An unacceptable proficiency testing result requires investigation of the root cause, documentation, and corrective action to address any identified problem. Proficiency testing specimens must be handled like patient specimens and records retained.

Question 40Quality improvement, quality control, quality assurance and ethical, legal, and regulatory issues relating to molecular genetic laboratory testing

Which of the following best characterizes the ethical obligation regarding incidental findings in clinical genomic testing?

  1. Only findings related to the original indication may ever be reported
  2. Incidental findings should be posted publicly for transparency
  3. Incidental findings should always be withheld from patients
  4. Laboratories and clinicians should have a defined policy for disclosure consistent with patient preferences and professional guidance Correct answer.

Explanation

Management of incidental findings should follow a defined policy that considers patient preferences, clinical actionability, and professional guidance. Neither blanket withholding nor public posting is appropriate.

Question 41Quality improvement, quality control, quality assurance and ethical, legal, and regulatory issues relating to molecular genetic laboratory testing

A laboratory uses an electronic health record interface to transmit results. Which control most directly supports data integrity in this process?

  1. Interface validation with audit trails and error checking Correct answer.
  2. Relying on verbal communication of critical results
  3. Disabling result timestamps to reduce clutter
  4. Manual re-entry of results by the receiving clinician

Explanation

Interface validation, audit trails, and error checking help ensure that results transmitted electronically remain accurate and traceable. Manual re-entry, verbal-only communication, and removal of timestamps increase risk of error.

Question 42Quality improvement, quality control, quality assurance and ethical, legal, and regulatory issues relating to molecular genetic laboratory testing

Which of the following is a recognized purpose of an internal audit within a molecular laboratory quality program?

  1. To replace external accreditation inspections
  2. To verify that processes conform to planned arrangements and are effectively implemented Correct answer.
  3. To assign blame to individual staff members
  4. To generate marketing material for the laboratory

Explanation

Internal audits verify that quality processes conform to planned arrangements and are effectively implemented, supporting continual improvement. They are not tools for assigning blame, replacing accreditation, or marketing.

Question 43Quality improvement, quality control, quality assurance and ethical, legal, and regulatory issues relating to molecular genetic laboratory testing

A clinician requests that a laboratory add a germline variant to a report based on a family member's known result without testing the patient. What is the most appropriate laboratory response?

  1. Add the variant based on the family history alone
  2. Explain that the variant cannot be reported without appropriate patient testing and offer testing options Correct answer.
  3. Report the variant as a provisional finding without documentation
  4. Refuse all communication with the clinician

Explanation

Laboratory results must be based on testing of the patient's specimen; reporting a variant inferred from family history without testing is not appropriate. The laboratory should explain the requirement and offer appropriate testing pathways.

Question 44Quality improvement, quality control, quality assurance and ethical, legal, and regulatory issues relating to molecular genetic laboratory testing

Which of the following best describes the concept of a reportable range in assay validation?

  1. The list of insurance payers accepted by the laboratory
  2. The interval of analyte concentrations or values over which the assay demonstrates acceptable performance Correct answer.
  3. The range of patient ages eligible for testing
  4. The number of specimens processed per shift

Explanation

The reportable range (analytical measurement range) is the interval over which the assay's results are demonstrated to be accurate and reliable. It is unrelated to patient age eligibility, throughput, or payer lists.

Question 45Quality improvement, quality control, quality assurance and ethical, legal, and regulatory issues relating to molecular genetic laboratory testing

A laboratory identifies a trend of increasing contamination in a molecular amplification workflow. Which quality tool is most appropriate to systematically investigate contributing factors?

  1. A root cause analysis Correct answer.
  2. A personnel performance review
  3. A billing reconciliation
  4. An equipment purchase order

Explanation

Root cause analysis is a structured method to identify underlying causes of a quality problem and guide corrective actions. Billing, personnel review, and purchasing do not systematically address the contamination process.

Question 46Quality improvement, quality control, quality assurance and ethical, legal, and regulatory issues relating to molecular genetic laboratory testing

Which statement best reflects the requirement for documenting competency assessment of molecular laboratory personnel?

  1. Competency assessment is optional for experienced staff
  2. Competency is demonstrated only by years of experience
  3. Competency is assessed initially and at defined intervals according to regulatory and accreditation standards Correct answer.
  4. Competency is assessed once at hire with no further requirement

Explanation

Regulatory and accreditation standards require competency assessment at defined intervals after initial evaluation, not merely at hire or as an optional activity. Years of experience alone do not satisfy documented competency requirements.

Question 47Quality improvement, quality control, quality assurance and ethical, legal, and regulatory issues relating to molecular genetic laboratory testing

A laboratory is considering a change in its analytic pipeline software that could affect variant calling. What quality step is most appropriate before clinical implementation?

  1. Perform verification testing to confirm performance is maintained after the change Correct answer.
  2. Suspend all testing permanently
  3. Implement immediately and monitor for errors
  4. Rely on the vendor's assurance that the change is minor

Explanation

Changes to software affecting analysis require verification to confirm that performance is maintained before clinical use. Immediate unverified implementation, reliance on vendor assurances alone, or indefinite suspension are not appropriate.

Question 48Quality improvement, quality control, quality assurance and ethical, legal, and regulatory issues relating to molecular genetic laboratory testing

Which of the following best describes the purpose of a chain-of-custody procedure in a molecular laboratory?

  1. To document the chronological handling of a specimen to maintain its integrity and traceability Correct answer.
  2. To schedule staff rotations
  3. To determine the billing code for a test
  4. To select the appropriate assay chemistry

Explanation

Chain of custody documents the chronological handling and transfer of specimens to preserve integrity and traceability, which is important for certain legal and forensic contexts. It does not determine billing, chemistry selection, or staffing.

Question 49Quality improvement, quality control, quality assurance and ethical, legal, and regulatory issues relating to molecular genetic laboratory testing

A patient's genetic test result is requested by a third party. Under typical privacy principles, what is the most appropriate laboratory action?

  1. Refuse all releases regardless of authorization
  2. Verify authorization and release only as permitted by law and applicable policy Correct answer.
  3. Release the result to any requester without verification
  4. Post the result on a shared portal accessible to all staff

Explanation

Release of genetic results to third parties requires verification of authorization and compliance with applicable privacy law and policy. Unrestricted release or blanket refusal ignores lawful authorization processes, and public posting violates privacy.

Question 50Quality improvement, quality control, quality assurance and ethical, legal, and regulatory issues relating to molecular genetic laboratory testing

Which of the following is an appropriate element of a laboratory's quality assurance program for molecular testing?

  1. Periodic review of quality indicators and trending of errors and corrective actions Correct answer.
  2. Use of a single control result with no monitoring over time
  3. Restricting quality review to annual accreditation visits only
  4. Elimination of all documentation to reduce workload

Explanation

Quality assurance involves ongoing monitoring through quality indicators, trending of errors, and evaluation of corrective actions. It is continuous rather than limited to accreditation visits, and documentation is essential.