Genome Sequencing

General Information

Lab Name

Genome Sequencing

Lab Code

GNOME

Description

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.

Forms & Requisitions

GSTL Exome and Genome Requisition

Components

Code	Name
GXRES	Genome Sequencing Result

Interpretation

Guidelines

Genetics and Solid Tumor Diagnostic Testing

Method

Next generation DNA sequencing is performed to identify small variants (SNV and INDEL), copy number variants >1 Kb, regions of homozygosity, and repeat expansions of select genes: AR, ATN1, ATXN1, ATXN2, ATXN3, ATXN7, ATXN10, C9ORF72, CACNA1A, COMP, CSTB, DMPK, FMR1, FXN, GLS, HOXD13, HTT, JPH3, PABPN1, PHOX2B, PPP2R2B, TBP, and ZIC2. Mitochondrial genome analysis is performed concurrently. Genomes are sequenced to an average read depth of 35x and compared to the GRCh38 human genome reference and the revised Cambridge Reference Sequence. Sequence alignment and variant detection are performed using Illumina’s DRAGEN pipeline. All called variants are assigned a quality score for filtering. Variants are assessed for pathogenicity using available information from population, clinical, and genetic resources. Variant prioritization and analysis are performed in Emedgene software (Illumina).

Reference Range

See individual components

Interferences and Limitations

Some types of variation are not reliably detected by this assay, including mosaic variants with allele frequencies lower than 20%, complex structural variants, nucleotide repeat expansions or contractions outside the targeted genes analyzed, DNA methylation, and, rarely, misannotated variants due to limitations in variant calling. Variants occurring in regions containing paralogous genes, pseudogenes, repeat or homopolymer tracks, high GC content, or otherwise low coverage, may impair the accuracy of the results.

Ordering & Collection

Specimen Type

Blood, saliva, cultured amniocytes or chorionic villus cells, extracted genomic DNA from a CLIA certified lab. Please contact the Genetics laboratory at 206-598-1149 to request a saliva kit (Oragene Dx OGD-500 or OGD-575 assisted collection). Direct chorionic villi, amniocyte, or amniotic fluid testing requires Genetics Director approval. Please call the lab at 206-598-7021 for approval.

Collection

Acceptable:

Whole blood: 5 mL lavender top (EDTA) tube or yellow (ACD) top tube or 2 mL microtainer lavender top tube.
Extracted DNA from blood, chorionic villi, and amniocytes: 500 ng (concentration >10 ng/uL).
Cultured amniocytes/chorionic villi: MCC is required for testing fetal samples. See Maternal Cell Contamination, Fetal [MCC].
Saliva (collected from Oragene Dx OGD-500 or Oragene Dx OGD-575 assisted collection). Please contact the Genetics laboratory at 206-598-1149 to request a kit.

*NOTE: If a fetal sample (cultured amniocytes or chorionic villi) was received, add MCC to the order. Prenatal testing requires concomitant testing for maternal cell contamination (see Online Test Guide, Maternal Cell Contamination, Fetal [MCC] for ordering and specimen requirements). See Special Instructions.

Unacceptable: Heparin green top tubes, buccal swab

Forms & Requisitions

GSTL Exome and Genome Requisition

Quantity

Requested: Entire sample
Minimum: Blood: 1 mL. If volume is less than 1mL, do not cancel. Send to Genetics lab. Confluent cultured cells: One (1) T25 flask. Extracted DNA: 250 ng

Processing

Receiving Instructions

SPS specimen handling:

Whole blood sample: store in the refrigerator
Cultured amniocytes/chorionic villi: store at room temperature. Call the Genetics lab upon receipt (206)598-7021.
Extracted DNA: store in the refrigerator
Saliva: store at room temperature

If fetal tissue (cultured amniocytes or chorionic villi) was received for prenatal testing, consultation with the laboratory is required. Please notify the Genetics lab about prenatal studies via email at geneticshelp@uw.edu or call 206-598-7021.

Note: Please include clinical history.

Misc Sendout

Performance

Lab Department

Genetics(GEN)

Frequency

Results within 4-6 weeks.

Available STAT?

Performing Location(s)

UW-MT	Genetics Attention: Genetics Lab Clinical lab, Room NW220 University of Washington Medical Center 1959 NE Pacific Street Seattle, WA 98195 Tel: 206-598–6429 M–F (7:30 AM–4:00 PM) Fax: 206-616-4584 Lab email: cgateam@uw.edu Tel (EXOME only): 206-543-0459	Faculty Jillian Buchan, PhD, FACMG Runjun Kumar, MD, PhD Regina Kwon, MD, MPH Christina Lockwood, PhD, DABCC, DABMGG Candace Myers, PhD Colin Pritchard, MD, PhD Vera Paulson, MD, PhD Eric Konnick, MD, MS He Fang, PhD Ghayda Mirza, MD Kristyn Galbraith, MD Annie Garcia, MD Karen Chisholm, MD, PhD

Billing & Coding

LOINC: 86206-0
Interfaced Order Code: UOW6333
Billing Comments: Billing Comments

For additional test/billing information, see following page: Genome Sequencing Billing.

For pricing information, contact Client Support Services 206-520-4600 or 800-713-5198.

We offer insurance preauthorization services (preauthorization is only done for providers who are external to the UW system).

Email: gpab@uw.edu or call 1-855-320-4869 for more information.

Genetics Preauthorization Form