Assessment for clinical genetic testing laboratories covering CLIA high-complexity testing, FDA LDT oversight, and genetic counseling requirements
CLIA certificate: Molecular genetic testing classified as high-complexity; requires qualified director, technical supervisor
Director qualifications: Board certification in molecular genetics OR doctoral degree with training/experience
Personnel: Bachelor degree + 2 years experience OR master degree + 1 year for high-complexity testing
Analytical validation: Limit of detection, accuracy (concordance with reference method), precision (repeatability, reproducibility)
Reportable range: Minimum 3 positive and 3 negative samples at each decision point; variant allele frequency (VAF) thresholds
Interference testing: Hemolysis, lipemia, bilirubin; cross-reactivity with related sequences (pseudogenes, homologs)
Clinical validity: Published literature, population studies; distinguish pathogenic from benign variants
ACMG variant classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign (5-tier system)
VUS reporting: State insufficient evidence for classification, may be reclassified with new data, clinical correlation needed
Report elements: Test method, genes/regions analyzed, genome build (GRCh37/38), coverage metrics, limitations
ACMG Secondary Findings: 78 genes for actionable conditions; opt-in/opt-out consent required
Genetic counseling: Recommend for positive results, cascade testing of relatives, reproductive implications
Informed consent: Written documentation, benefits/risks, VUS possibility, insurance discrimination (GINA), psychological impact
Genetic counseling: Certified counselor (GC) or physician with genetics training; discuss results, family implications
Privacy: HIPAA compliance, GINA protections, state genetic privacy laws, data retention policies
QC controls: Known positive sample, wild-type negative, reagent blank; acceptance criteria defined
PT: CAP Surveys or alternative; blinded samples, no conferring, failure investigation within 30 days
Variant databases: ClinVar for clinical significance, HGMD for published variants, population databases (gnomAD)
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