Specialist in Molecular Biology (SMB) Exam Prep
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Free SMB Practice Questions

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The SMB exam has 100 questions and runs 2 hours 30 minutes.

These 10 free SMB questions are organized by exam domain, so you can see how each part of the Specialist in Molecular Biology (SMB) blueprint is tested. Reveal the answer and explanation under each question.

Domain 1: Molecular Science (5-10%)

Question 1

A substitution at the final nucleotide of exon 6 is synonymous when assessed against the reference coding sequence. Patient cDNA sequencing nevertheless shows exon 5 joined directly to exon 7. Genomic testing confirms that exon 6 has normal copy number. Which molecular mechanism reconciles the DNA and RNA findings?

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Correct answer: C - Disruption of exon recognition during pre-mRNA splicing

Domain 2: Molecular Techniques (30-35%)

Question 2

A whole-blood DNA extract gives no target signal in a real-time PCR assay. Each reaction receives the same amount of a noncompetitive exogenous amplification control after any sample dilution. In the undiluted extract, the control has a Cq of 38. After a 1:5 dilution, the control has a Cq of 29 and the patient target becomes detectable at Cq 33. The uninhibited control also has a Cq of 29, and negative controls remain negative. What accounts for the recovery of both signals?

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Correct answer: B - Dilution lowers the inhibitor concentration enough to restore amplification of both targets.

Question 3

A hereditary-cancer NGS panel passes run-level quality checks, and no reportable variants are found. One BRCA1 exon has only 12 unique reads, although their base-quality scores exceed Q30. The laboratory requires at least 50 unique reads to make a negative sequence-variant call for that exon. All other regions meet their validated requirements, and the reporting procedure permits region-specific coverage limitations. Which reporting approach is justified?

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Correct answer: B - Report findings for adequately covered regions and explicitly identify the BRCA1 exon as a coverage gap.

Question 4

A bisulfite-sequencing assay suggests promoter methylation in a tumor. However, a fully unmethylated control processed alongside the specimen retains cytosines at several conversion-control positions expected to read as thymine. Template identity checks and sequencing quality are acceptable. Which failure most directly threatens the methylation interpretation?

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Correct answer: C - Incomplete conversion of unmethylated cytosines

Domain 3: Laboratory Operations (25-30%)

Question 5

An RNA-extraction waste bottle contains human specimen lysate mixed with a guanidinium thiocyanate buffer. A technologist is about to add sodium hypochlorite before disposal; no disinfectant has yet been added. Which intervention prevents the immediate chemical hazard?

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Correct answer: A - Keep hypochlorite out; follow the designated procedure for mixed chemical/biological waste.

Question 6

In a comparison of two quantitative molecular assays, 80 patient specimens spanning the measurement range produce a correlation coefficient of 0.998. The candidate method nevertheless reads approximately 30% higher across the range, while replicate precision is acceptable. A supervisor argues that the methods are interchangeable because their correlation exceeds 0.99. What flaw defeats that argument?

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Correct answer: D - Closely correlated results can still have a systematic proportional difference.

Domain 4: Applications of Molecular Testing (35-40%)

Question 7

A patient with previously confirmed BCR::ABL1-positive chronic myeloid leukemia has follow-up marrow testing during therapy. Interphase FISH detects no fusion in 200 nuclei, while RT-qPCR detects the patient's known e14a2 transcript at 0.04% on the International Scale. RNA quality and all controls are acceptable, and the PCR result is within the assay's validated quantitative range. At sign-out, how should the apparent discrepancy be handled?

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Correct answer: D - Report both findings; low-level residual transcripts can remain detectable after FISH becomes negative.

Question 8

A hospitalized adult develops diarrhea after antibiotic exposure. A promptly processed stool specimen is positive for the Clostridioides difficile toxin B gene by NAAT but negative by toxin immunoassay. All assay controls pass. The treating physician asks whether the molecular result establishes active C. difficile infection. What is the most accurate reply?

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Correct answer: A - Toxin-gene DNA is detected; active infection still requires clinical assessment.

Question 9

Pharmacogenetic testing before clopidogrel therapy following coronary stent placement identifies CYP2C19 *2/*17. The *2 allele has no function, whereas *17 has increased function. How should this diplotype be translated for clopidogrel?

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Correct answer: C - Intermediate metabolizer; formation of clopidogrel's active metabolite is reduced.

Question 10

A 7-year-old boy with intellectual disability undergoes FMR1 testing. A repeat-sizing assay identifies an allele containing approximately 280 CGG repeats, and methylation analysis demonstrates abnormal promoter methylation. How should this allele be classified and interpreted?

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Correct answer: B - An FMR1 full mutation associated with methylation-mediated transcriptional silencing

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