ABMGG Molecular Genetic Pathology key terms

The lowest analyte amount or variant allele fraction that an assay can reliably distinguish from background, established experimentally with replicates and usually reported at a stated confidence level.

The highest signal expected from a specimen containing no analyte, derived from repeated measurements of blank samples and used as the baseline for setting the limit of detection.

The ability of a test to measure only the intended analyte, avoiding cross-reactivity with related sequences, organisms, or variants that could produce a false-positive result.

The ability of an assay to detect small amounts of the target analyte; distinct from clinical sensitivity, which describes how often the test is positive in people who truly have the condition.

The strength of evidence linking a test result to a clinical condition or outcome, describing how well the assay predicts disease presence, risk, or treatment response in the intended population.

Evidence that using a test changes patient management and improves outcomes compared with not using the test, going beyond mere association between result and disease.

External assessment in which a laboratory tests blinded samples of known composition and its results are compared with peer laboratories or a reference method to demonstrate ongoing competence.

Routine internal monitoring of assay performance using samples with known expected results, run alongside patient specimens to detect shifts, drift, or random error before results are released.

A well-characterized substance or sample with assigned property values, used to calibrate assays, validate performance, or verify measurement traceability, ideally certified by an authoritative body.

The proportion of sequencing reads or signal at a locus that carries a specific variant, reflecting the fraction of alleles with the change in the tested sample.

Age-related expansion of a blood cell clone carrying a somatic mutation, typically at variant allele fraction above 2%, without diagnostic criteria for a hematologic malignancy.

Detection of small numbers of neoplastic cells remaining after treatment, below the threshold of routine morphology, using sensitive molecular or flow-based methods to assess depth of response.

The number of somatic coding mutations per megabase of tumor DNA, an emerging biomarker for immunotherapy response that depends heavily on assay panel size and bioinformatic pipeline.

Length variation in short tandem repeat sequences caused by defective DNA mismatch repair, detected as altered repeat sizes in tumor DNA compared with normal tissue.

Loss of function in DNA mismatch repair proteins, arising from germline or somatic gene inactivation or silencing, leading to a hypermutable phenotype detectable by immunohistochemistry or microsatellite testing.

A germline or somatic sequence change whose association with disease has not been established, so it should not be used clinically to guide management without further evidence.

A sequence alteration with sufficient evidence to cause or strongly predispose to a disease, supporting clinical action such as surveillance, treatment, or family testing.

A framework using weighted criteria such as population frequency, computational prediction, segregation, and functional data to categorize variants as pathogenic, likely pathogenic, uncertain, likely benign, or benign.

The proportion of chromosomes in a population that carry a given allele, used to judge how common a variant is and to help distinguish benign polymorphisms from disease-causing changes.

The proportion of individuals carrying a disease-associated genotype who show the associated phenotype, which may be age-dependent and influenced by modifying genes or environment.

Loss of one allele at a locus, often through deletion or copy-neutral change, leaving only the remaining allele; a common mechanism unmasking recessive cancer genes or revealing tumor clonality.

A gain or loss of genomic sequence, ranging from a single exon to whole chromosomes, detected by dosage-sensitive methods such as array comparative genomic hybridization or read-depth analysis.

A cytogenetic technique using fluorescently labeled probes that hybridize to specific chromosomal regions in fixed cells, allowing detection of deletions, amplifications, and rearrangements in interphase or metaphase nuclei.

A full description of an individual's chromosome complement obtained by staining and ordering condensed chromosomes, detecting numerical and large structural abnormalities at roughly five to ten megabase resolution.

A genome-wide platform of probes that measures copy number and, with SNP content, loss of heterozygosity and regions of homozygosity, used as a first-tier test for developmental disorders.

A short random sequence tag attached to individual DNA molecules before amplification, allowing bioinformatic collapse of duplicate reads to correct for PCR bias and improve variant detection at low allele fractions.

Partitioning a sample into thousands of tiny reactions so each contains zero or a few template molecules, then counting positive partitions to give absolute quantification without a standard curve.

Repeated cycles of denaturation, primer annealing, and extension with a thermostable polymerase to exponentially amplify a target sequence, forming the basis of most molecular diagnostic assays.

PCR monitored during each cycle using fluorescent reporters, where the cycle at which signal crosses a threshold reflects starting template amount, enabling relative or absolute quantification.

The PCR cycle number at which the fluorescence signal first exceeds a defined background threshold; lower values indicate more starting target, but values are not comparable across different assays.

The temperature at which half of a primer-target duplex dissociates, determined largely by length and guanine-cytosine content and used to design primers that anneal at compatible temperatures.

The combined conditions, especially temperature and salt concentration, that determine how strictly complementary sequences must be to hybridize, allowing discrimination of closely related sequences.

Base-pairing between complementary nucleic acid strands, exploited in assays such as Southern blotting, microarrays, and in situ probes to detect specific sequences.

Massively parallel sequencing methods that read millions of DNA fragments simultaneously, producing short or long reads that are aligned to a reference to detect variants and quantify abundance.

The average number of sequencing reads covering a given base, which determines the power to detect variants and is often reported alongside the minimum depth at a locus.

The bioinformatic process of comparing aligned sequencing reads with a reference to identify positions where the sample differs, assigning quality scores and filtering artifacts.

Assigning biological meaning to a detected variant, including transcript consequence, population frequency, predicted effect, and known clinical significance, typically through curated databases and software.

Dideoxy chain-termination sequencing that resolves labeled fragments by capillary electrophoresis, still used as the confirmatory standard for single-nucleotide variants and short indels.

The study of how inherited genetic variation influences drug metabolism, transport, or target response, used to select drugs and doses likely to be effective and safe for an individual.

A named haplotype designation for a pharmacogene that bundles multiple sequence variants into a single allele, with each star number indicating a defined set of changes and function.

Converting detected diplotypes into a predicted metabolic activity score or phenotype category, such as poor, intermediate, normal, or rapid metabolizer, used to guide drug dosing.