Summary: Provides a quick reference for the detection capabilities of common types of genetic testing, such as gene sequencing and deletion/duplication analysis.
By JAX Clinical Education |August 2025
Targeted mutation analysis: Targeted tests that assess specific variants within a gene or genes that have been associated with a condition. For example, testing for a specific variant that has been identified as pathogenic in a close relative. Some carrier screening tests for reproductive planning are targeted to specific variants.
Condition-specific tests: Tests for a specific genetic condition of interest, comprehensively, often using multiple methods to detect different variant types associated with the condition (e.g., hereditary ataxia evaluation, sensorineural hearing loss panel, Cowden syndrome testing). They may include testing for one or multiple genes, depending on the condition.
Broad multi-gene panels: Tests for variants in genes associated with a condition or category of conditions (e.g., infantile epilepsy panel, hereditary cancer panel). They may or may not include multiple testing methods to detect different variant types. Includes multiple genes, ranging from a few to dozens.
Exome sequencing: The exome is the portion of the genome containing the protein-coding regions of the genes known as exons. While representing only about 1% of the genome, exome sequencing has a high diagnostic yield because most variants known to be associated with hereditary conditions are located within the exons, or in the regions immediately flanking them.
Genome sequencing: Examines nearly all coding and non-coding DNA, or about 3 billion base pairs of DNA, and results in a very large amount of data that needs to be interpreted. It includes assessment of the non-coding and regulatory regions of the genome, where a variant associated with disease could possibly be located.
Chromosome analysis (karyotype): Analysis of the structure of chromosomes. It detects extra or missing chromosomes and large structural arrangements. It can detect deletions as small as 3-5 Mb and duplications larger than ~5 Mb.
Chromosomal microarray analysis (CMA): Test that is used to detect deletions and duplications by assessing copy number variation. CMA is sensitive for deletions and duplications as small as 100kb.
Single nucleotide variants (SNV): Changes to a single nucleotide within the DNA sequence, such as single base substitutions, insertions, or deletions.
Deletions and duplications. Missing or extra genomic information. Both very small (single nucleotides) and very large (whole chromosomes) insertions and deletions of genomic information can impact gene function.
Indel (insertion/deletion) is the term typically used for deletions and duplications of less than 1 kb, or 1000 bases (nucleotides).
CNV (copy number variation) is typically used for deletions and duplications of more than 1 kb. CNVs can be as large as an entire chromosome (e.g., Down syndrome).
Trinucleotide repeat (TNR) expansion: A type of duplication with three specific nucleotides recurring multiple times in a row, beyond what is normally expected in a given area of a gene (e.g., Friedreich ataxia).
Methylation: The addition of methyl groups to DNA can turn the activity of a gene off. Changes to the methylation pattern can cause disease (e.g., imprinting disorders such as Angelman syndrome). These changes do not change the DNA sequence.
Mitochondrial DNA variants (mtDNA): Changes to the DNA in the mitochondria can include single nucleotide variants and deletion/duplications (e.g., mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes or MELAS).
Tests vary significantly among laboratories. The table below indicates variant types that are commonly assessed with each test type. While labs will assess certain variant types appropriate for the condition, check with the lab to determine which variants can be detected by their specific test.
Table 1: Comparison of tests and the variants commonly assessed in each of the test types | ||||||
| SNV | Indel | CNV | TNR | Methyl | mtDNA |
Targeted mutation analysis | X | X | X | X | X | X |
Condition-specific | X | X | X | X | X | X |
Broad multi-gene tests | X | X |
| |||
Exome sequencing | X | X |
|
|
| |
Genome sequencing | X | X | | X | ||
CMA | X* | X |
| X | ||
* CMA is only able to detect deletions and duplications greater than 100kb, and the exact size depends on the specific CMA methodology used.
In general, as the scope of a genomic test increases:
Scope: The specific subset of genetic material the test assesses.
Sensitivity: Includes both whether certain types of variants are detected and, for sequence variants, the read depth (the number of times a particular base is assessed). Read depth can be an important factor impacting the interpretation of wide-scale tests such as exome and whole genome testing, as it indicates the likelihood that the test would have identified a variant if it was present.
Uncertain: Occur when a test detects variants for which their impact and/or specific function remain unknown or unclear.
Secondary: Identification of variants in genes unrelated to the presenting condition. These findings may or may not be reported, depending on lab policies and procedures and patient preferences. They may have important clinical consequences, such as identification of hereditary cancer risk.
Unexpected: Identification of variants that indicate misattributed family relationships (e.g., nonpaternity), or variants in genes not previously suspected, but related to the presenting findings.
Genetic Testing in Pediatric Neurology. Practice identifying when further value might be added by a molecular diagnosis and choosing the best genetic tests for the clinical context.
Genomic Testing for Diagnosis (CME|CNE). Practice identifying patients who may benefit from genomic testing and communicating with patients, families, and genetic experts about testing.
All information in this resource is provided for educational purposes only.