AGMT study plan

Map each major testing methodology (PCR/qPCR, Sanger sequencing, NGS panels, exome/genome, microarray, MLPA, karyotype/FISH) to the variant classes and clinical questions it best answers

Explain the chemistry of Sanger sequencing and the NGS sequencing-by-synthesis cycle step by step without notes

Distinguish analytical sensitivity, specificity, and limit of detection for each platform and state which specimens each tolerates

Build a comparison table of platforms by turnaround time, cost tier, and residual risk of missed variants

Trace a germline NGS workflow from accessioning through library prep, sequencing, alignment, variant calling, and orthogonal confirmation, naming the QC failure point at each step

Calculate expected coverage, limit of detection, and variant allele fraction thresholds for a given read depth scenario

Explain when orthogonal confirmation (Sanger, qPCR, MLPA) is required versus optional and justify the reasoning

Compare specimen types (blood, saliva, buccal, FFPE, cfDNA) for nucleic acid quality constraints and pre-analytical failure modes

Describe DNA replication, transcription, and translation and locate where each common variant class disrupts gene function

Classify variant types (missense, nonsense, frameshift, splice-site, copy-number, repeat expansion, structural) and predict their molecular consequence

Explain the mechanisms of trinucleotide repeat instability and anticipation using a named locus

Summarize epigenetic mechanisms (methylation, imprinting) and how they produce disease without a sequence change

Describe chromosome structure, banding nomenclature (ISCN), and the resolution limits of G-banding versus FISH versus microarray

Distinguish constitutional from acquired cytogenetic abnormalities and give two clinical examples of each

Explain the detection capabilities and blind spots of CMA (balanced events, low-level mosaicism, polyploidy)

Interpret a written karyotype string and a written microarray result into a plain-language clinical statement

Work through autosomal dominant, autosomal recessive, X-linked, and mitochondrial pedigrees and assign correct recurrence risks

Apply Bayes-style reasoning to update carrier risk given family history and a negative or uncertain test result

Explain penetrance, variable expressivity, anticipation, and consanguinity as risk modifiers

Relate testing strategy choice (carrier, diagnostic, predictive, prenatal) to the inheritance pattern and the clinical question

Match clinical scenarios (suspected hereditary cancer, cardiac sudden death, developmental delay, prenatal anomaly, pharmacogenomic decision) to the appropriate first-line test

Explain the difference between diagnostic, predictive, carrier, and prenatal testing and state the pre-test counseling implication of each

Identify when a negative result is uninformative versus truly negative based on the test's coverage and the phenotype

Describe how a variant of uncertain significance is managed clinically and what evidence would reclassify it

Apply ACMG/AMP variant classification criteria and assign a class to 5 provided variant descriptions with justification

Explain database and tool limitations (population frequency, in silico predictors, segregation data) and when each should be weighted

Outline a quality management system: document control, competency assessment, proficiency testing, and validation requirements for a new assay

Distinguish the roles of CLIA, CAP, and FDA oversight for laboratory-developed tests

Apply informed consent, confidentiality, and duty-to-warn principles to three written ethical scenarios and defend a position

Explain GINA protections and their gaps for life, disability, and long-term care insurance

Identify incidental/secondary findings policy considerations and the patient's right to opt out

Execute a full-length timed practice exam and categorize every missed item by domain to direct final review