| | Individual gene sequencing | Gene panel | Exome sequencing | Genome sequencing | Chromosomal microarray analysis |
| Strengths | - Lowest overall cost
- Fast result time
- High accuracy
| - Rapid sequencing of multiple genes
- Decreased secondary findings compared with exome/genome sequencing
- Possible detection of pathogenic noncoding variants or mosaicism
| - "Unbiased"
- Possible discovery of new genes that cause disease
- Possible identification of conditions caused by defects in multiple genes
| - "Unbiased"
- Identification of variants in noncoding regions
- Possible discovery of new genes that cause disease
- Possible identification of conditions caused by defects in multiple genes
- Identification of SVs/CNVs possible
| - Detection of CNVs
- Fast result time
|
| Limitations | - Poor or no detection of:
- CNVs and SVs
- Portions of the gene not included in the assay
| - No detection of genes or gene regions that are not on the panel
| - Lower coverage of noncoding regions results in lower likelihood of detection of variants in noncoding regions
- High likelihood of detecting variants of uncertain significance and incidental findings
| - Highest cost
- High likelihood of detecting variants of uncertain significance and incidental findings
- Current analysis of noncoding regions is limited, resulting in large numbers of potential candidate variants
| - Poor or no detection of:
- Single nucleotide variants
- Very small duplications and deletions or chromosomal rearrangements that do not affect the nucleotide copy number
|
| Expert recommendations | - Use when a single genetic etiology is suggested
- Consider for testing of family members
- Should be performed for technical confirmation of findings detected by the other methods
| - Use when rapid testing is needed for a confined list of gene candidates and/or high-sensitivity locus-specific interrogation is needed
| - Consider in patients with complex phenotypes or for whom a family history of consanguinity is suspected
- Use in tandem with CMA when a genetic diagnosis is absent or uncertain after single gene or gene panel testing
| - Consider when a genetic diagnosis is strongly suspected but has not been identified by the other genomic approaches
| - Consider as an initial test when the phenotype is too nonspecific to suggest a narrow list of genetic etiologies
- Use to complement gene panel or exome sequencing
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