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Physician Board Certification

ABPath Molecular Genetic Pathology Subspecialty Certification Examination Practice Test

Molecular genetic pathology interprets DNA and RNA findings in inherited disease and cancer, linking laboratory results with clinical context. The available practice material includes variant classification, sequencing limitations, specimen quality, family-based analysis, and the interpretation of RNA-based fusion findings.

Exam overview

Exam providerAmerican Board of Pathology
Exam codeNot listed
CategoryPhysician Board Certification

About the ABPath Molecular Genetic Pathology Subspecialty Certification Exam… Exam

Questions in this area call for careful appraisal of evidence rather than reliance on a variant label alone. Relevant reasoning includes weighing phenotype fit and supporting data, recognizing how trio analysis can identify a de novo variant, and distinguishing a negative result from exclusion of disease when an assay cannot detect a suspected variant class. Laboratory decisions also involve preserving RNA, assessing tumor content in formalin-fixed tissue, and considering technical blind spots such as structural or copy-number changes. Reporting tasks include describing variants precisely enough for consistent interpretation. RNA sequencing can demonstrate an expressed fusion transcript, but that finding does not by itself define the underlying genomic rearrangement. These concepts connect assay capabilities, specimen limitations, inheritance, and clinical interpretation.

Sample Practice Questions

Review a selection from this exam's published US Practice Tests practice bank.

Question 1

A laboratory identifies a likely pathogenic variant in a gene, but the patient's phenotype is atypical and no other supporting evidence is available. Which principle should guide interpretation?

  1. AIntegrate population, computational, functional, segregation, and phenotype evidence using a structured classification framework
  2. BClassify the variant as pathogenic solely because it is rare
  3. CAssume any protein-altering variant is disease-causing
  4. DUse the patient's diagnosis to override all assay quality concerns
Show answerCorrect answer: A

Variant classification should integrate multiple evidence types in a structured framework. Rarity or predicted protein impact alone is insufficient, and phenotype fit and technical validity remain important considerations.

Question 2

A molecular laboratory receives a specimen for a test that requires intact RNA. Which collection and handling approach best supports RNA integrity?

  1. AUse the validated RNA-stabilizing collection system and follow the assay-specific transport and processing requirements
  2. BPlace the specimen in any routine fixative and store it at room temperature
  3. CDelay processing until the specimen has undergone repeated freeze-thaw cycles
  4. DAdd a DNA-binding dye before transport
Show answerCorrect answer: A

RNA is vulnerable to degradation by RNases and suboptimal handling. Using the validated collection system and adhering to specified transport, temperature, and processing conditions helps preserve RNA quality for testing.

Question 3

A laboratory performs trio exome sequencing for a child with a suspected de novo genetic disorder. Which result is most consistent with a de novo variant?

  1. AThe variant is present in the child and absent from both parents, with parentage and assay limitations considered
  2. BThe variant is present in the child and in one unaffected parent
  3. CThe variant is absent from the child but present in both parents
  4. DThe variant is present only in the mother and is not assessed in the child
Show answerCorrect answer: A

A de novo variant is detected in the affected individual but not in either tested parent. Interpretation should account for technical limitations, possible parental mosaicism, and confirmation of biological relationships where relevant.

Question 4

A laboratory is preparing a clinical molecular report for a newly identified variant. Which information is most important to include so that the result can be interpreted unambiguously across laboratories and databases?

  1. AA standardized genomic or transcript-level variant description with reference sequence information
  2. BOnly the patient's initials and the laboratory's internal sample number
  3. CA description of the sequencing instrument model without the variant location
  4. DAn informal label based solely on the patient's phenotype
Show answerCorrect answer: A

Standardized variant nomenclature linked to an identified reference sequence supports reproducible interpretation, comparison, and database review. Internal identifiers, instrument details, or phenotype-based informal labels do not uniquely describe the variant.

Question 5

A laboratory performs RNA sequencing to evaluate a suspected gene fusion. The assay detects a fusion transcript, but the report must distinguish an expressed fusion from a genomic rearrangement that may not produce a stable transcript. What does the RNA result directly establish?

  1. AA fusion transcript containing the reported partner sequences is present in the tested RNA
  2. BThe rearrangement is present in every cell of the patient
  3. CThe fusion is necessarily inherited
  4. DThe genomic breakpoint has been fully resolved
Show answerCorrect answer: A

RNA-based detection demonstrates that the target fusion transcript is expressed in the tested sample, subject to assay design and quality. It does not by itself prove germline status, presence in every cell, or complete characterization of the genomic breakpoint.

Question 6

A child has a suspected disorder caused by a pathogenic variant in a gene with a known pseudodeficiency allele that can produce abnormal results in an enzyme assay. Which approach best helps distinguish pseudodeficiency from true disease?

  1. AInterpret the enzyme result alongside molecular findings and clinical features
  2. BDiagnose the disorder from the enzyme result alone in every case
  3. CIgnore molecular findings because pseudodeficiency affects all genetic tests
  4. DRepeat the same enzyme assay using the same specimen without further evaluation
Show answerCorrect answer: A

Pseudodeficiency can cause reduced measured enzyme activity without the corresponding clinical disease. Integrating biochemical results with molecular findings and phenotype helps distinguish true deficiency from assay-related pseudodeficiency.

Question 7

A patient with a suspected hereditary disorder has a negative result on a sequencing assay that does not evaluate repeat expansions. Which follow-up test class is most directly appropriate if the phenotype suggests a repeat-expansion disorder?

  1. AA repeat-expansion assay designed for the implicated locus
  2. BA routine karyotype with no targeted follow-up
  3. CA protein electrophoresis assay for all genes
  4. DA repeat of the same sequencing assay at greater depth
Show answerCorrect answer: A

Repeat expansions can exceed the size or sequence-context limits of conventional short-read sequencing. A locus-appropriate repeat assay, which may use methods such as repeat-primed PCR or another validated expansion-sizing approach, is needed to evaluate that variant class.

How to use this practice test

The free US Practice Tests bank contains 50 published questions; each session presents up to 20 random questions. Use a session to practice interpreting molecular findings and laboratory scenarios, then review the displayed results to identify which reasoning areas need more work.

Preparation tips

  • For variant interpretation, separate classification evidence from phenotype fit, segregation data, and other supporting or conflicting evidence.
  • Practice identifying what each assay can and cannot detect, including repeat expansions, structural variants, and possible second alleles in recessive disease.
  • Review specimen requirements for DNA and RNA testing, including collection, preservation, tumor enrichment, and the effects of formalin fixation.
  • Distinguish an expressed fusion transcript detected by RNA sequencing from proof of a specific genomic rearrangement.
  • Practice writing unambiguous variant descriptions and distinguishing a negative familial-variant result from a broad exclusion of genetic disease.
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