Genome Sequencing

Genome sequencing analyzes coding and non-coding regions of the genome to identify variation relative to a human reference sequence. The purpose of this test is to identify genetic variants that may explain the affected individual’s clinical features or disease.

Family member samples (comparators), typically the biological mother and biological father, can be included in this test to help identify potential candidate DNA changes. The inheritance information from biologically related individuals improves filtering of rare variants and increases the likelihood of identifying a clinically meaningful result.

Comparator samples must be received within 4 weeks. If comparator samples are not received, a change in the test codes will be required which can impact billing and prior authorization investigations.

Genome Singleton Sequencing (Proband-Only Whole Genome Sequencing) refers to genome sequencing performed on a single individual, typically the affected person (proband) without sequencing biological parents or other relatives. This approach analyzes both coding and non-coding regions of the genome to detect single nucleotide variants, small insertions/deletions, copy number variants, aneuploidy, regions of homozygosity, and repeat expansions. Mitochondrial genome sequencing is also performed. While this test can identify many clinically relevant variants, interpretation may be more challenging than family-based sequencing because inheritance patterns and de novo status cannot be evaluated.

Genome Sequencing with Comparators (Family-Based Whole Genome Sequencing) refers to genome sequencing performed on the affected individual along with one or more biologically related individuals (such as parents or siblings). The comparator samples are used to help interpret the proband’s genetic variants by determining inheritance patterns, including whether variants are inherited or occurred de novo. This approach improves variant interpretation, reduces the number of candidate variants, and increases the likelihood of identifying a clinically meaningful result by providing genetic context that is not available with proband-only sequencing.

Please indicate the number of samples being sent as comparators on the test requisition form. Genome sequencing is performed on comparator samples. Variants present in family members included in this analysis are not independently evaluated or reported.

Optional Secondary Findings in Medically Actionable Genes. If requested, the laboratory will report genetic variants unrelated to the primary indication for testing that are considered potentially medically actionable (termed "secondary findings"). This analysis evaluates for pathogenic or likely pathogenic variants in genes specified by the American College of Medical Genetics and Genomics (ACMG) Secondary Findings gene list, version 3.3 (Lee et al., 2025).

For further details on available testing, see Genetics and Solid Tumor Diagnostic Testing.