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Whole Exome Sequencing (WES+)

A comprehensive diagnostic sequencing test covering all protein-coding genes of the nuclear genome, full mitochondrial analysis, and genome-wide copy number assessment, powered by the Helix Exome® platform. Available as Proband, Duo, or Trio.

Turnaround

As soon as 3 weeks

Requery (SOQO)

As soon as 1 week

Genes Tested

All protein-coding genes + mitochondrial genome

Test Description

The Helix Whole Exome+ Sequencing test evaluates the coding regions of the human genome, including the mitochondrial genome, to identify genetic variants associated with the clinical features described at ordering. This test is available as Proband (EXPR1), Duo (EXDU1), or Trio (EXTR1). When parental samples are provided (using EPAR1 for ordering in the EHR), segregation analysis is performed to aid in variant interpretation. Mitochondrial genome analysis is included by default, with heteroplasmy detection at ≥2% for blood and buccal specimens and ≥3% for saliva. Genome-wide copy number analysis is also included to evaluate for clinically relevant copy number variants across the genome, independent of HPO terms.

Full Description (PDF)Sample Positive ReportSample Negative Report

Order This Test

Contact our clinical team to order this panel or learn more.

(855) 699-1933
clinicalsupport@helix.com

Indications for Testing

WES+ testing is indicated for patients with symptoms suspected to have a genetic cause. Appropriate clinical scenarios include, but are not limited to, symptoms affecting more than one part of the body, physical differences present from birth, delays in development or learning disabilities, neurological (brain and nervous system) conditions, autism spectrum disorder, a suspected inherited condition without a clear diagnosis, and previous genetic tests that did not provide a clear answer.

Methodology

This test utilizes next-generation sequencing to detect single nucleotide variants, insertions and deletions up to 20 bp, and copy number variants in genes associated with the clinical features described at ordering. Data is aligned to GRCh38 and analyzed using MANE and MANE Plus Clinical transcripts. The mitochondrial genome is sequenced and analyzed for variants. Genome-wide copy number analysis is also performed to detect clinically significant large-scale copy number changes, independent of the clinical features provided at ordering. Variant interpretation is performed in accordance with ACMG/AMP guidelines and ClinGen Variant Curation Expert Panel modifications.

Technical Specifications

Methodology

Exome+® NGS (exome capture + deep intronic coverage in key regions + relevant promoters and inversions).

Analytical Sensitivity (SNV)

> 99.9%

Analytical Sensitivity (Indel)

> 99%

Analytical Specificity

> 99%

CNV Sensitivity (multi-exon)

Majority of CNVs spanning ≥3 exons reliably detected

Coverage Depth

99% of clinically relevant regions at ≥20x

Mitochondrial Heteroplasmy Detection

≥2% (blood/buccal), ≥3% (saliva)

Digital Karyotype

Genome-wide SNP tiling for detection of chromosomal microdeletions

Genomic Build

GRCh38

Test Configurations

WES+ is available in three configurations to match the clinical scenario. Trio testing is recommended when both parents are available, as it maximizes diagnostic yield by identifying de novo variants.

ConfigurationProcedure CodeDescription
ProbandEXPR1Sequencing and analysis of a single affected individual. Appropriate when parental samples are unavailable.
DuoEXDU1Proband plus one parent. Parental sample aids in phase confirmation and inheritance classification.
TrioEXTR1Proband plus both parents. Enables identification of de novo variants and provides the highest diagnostic yield. Recommended configuration when both parents are available.
Parental Add-on (EHR)EPAR1Used for ordering parental samples via EHR integration when segregation analysis is required.

Genes Tested

All protein-coding genes in the human nuclear genome are sequenced. Analysis and reporting are guided by the clinical features (HPO terms) described at ordering. The mitochondrial genome is also analyzed.

Ordering Information

Turnaround Time

Typically 3 to 5 weeks from sample receipt (standard). Typically 1 to 3 weeks (requery).

Preferred Specimen

BD Vacutainer Whole Blood K2 EDTA Collection Tube 4mL · Mawi iSWAB®-DNA Collection Kit (SD-T-1200FXL). Saliva is also available as a limited offering.

Shipping Instructions

Specimens to arrive at Helix within 96 hours of collection at ambient temperature.

Clinical Description

Whole exome sequencing evaluates the protein-coding regions of the genome, which comprise approximately 1–2% of the genome but harbor an estimated 85% of disease-causing variants. This test is designed for individuals with clinical features suggestive of a genetic condition, including but not limited to developmental delay, intellectual disability, congenital anomalies, neurological conditions, and other suspected Mendelian disorders. The analysis is guided by the clinical features provided at the time of ordering. Identification of a pathogenic variant may establish a molecular diagnosis, may inform prognosis and management, and facilitate genetic counseling for the patient and their family members. Mitochondrial genome analysis and genome-wide copy number analysis are included by default. When parental samples are provided (Duo or Trio), segregation analysis is performed to aid in variant interpretation.

Frequently asked questions

When should I order WES+ instead of a gene panel?
WES+ should be considered when there is multi-system involvement, multiple congenital anomalies, or a differential diagnosis that is broad or not well-covered by a curated panel. It is also appropriate when prior targeted testing did not identify a genetic cause, or for conditions like epilepsy where relevant gene lists are rapidly evolving and targeted panels can quickly become out of date. For many patients with developmental delay, autism spectrum disorder (ASD), epilepsy, or unexplained neurological conditions, WES+ is an efficient first-line approach.
What makes this an Exome "Plus"?
WES+ includes enhanced coverage of clinically relevant genes, exon-level CNV detection, digital karyotype, full mitochondrial analysis, and evaluation of non-coding variants. In addition, Helix uses whole genome sequencing behind the scenes when needed for variant confirmation or complex analysis. This combination provides a more complete diagnostic picture than a standard exome alone.
What is your coverage depth across the exome?
Helix has focused over a decade of R&D to ensure uniformity in coverage across the exome, reflected in the close alignment of mean and median coverage values. We achieve consistent depth through a WGS-like preparation approach, ensuring reliable variant detection across all clinically relevant regions. This strategy ensures high callability across the entire assay. 99% of clinically relevant regions are covered at 20x or greater.
Do I need to submit medical records with my order?
Yes, supporting documentation demonstrating medical necessity and indication for the order is required. They can be securely emailed to billing@helix.com or faxed to +1-858-777-3670.
Do I need to order a Trio? Is a Proband order acceptable?
Trios are not required. Helix accepts Proband, Duo, and Trio orders. Trio testing increases diagnostic yield by enabling identification of de novo variants and clarifying inheritance patterns, and is recommended when both parents are available. If parental samples cannot be collected at the time of ordering, Helix will initially hold the proband sample if awaiting parental samples. To avoid further delays, though, the order will then be converted to Duo or Proband after a 3 week hold, based on which samples have been received by that time.
Is mitochondrial analysis included? What heteroplasmy level is detected?
Full mitochondrial genome analysis is included by default, based on the clinical notes provided, for every WES+ order and at no additional cost. Heteroplasmy is detected at ≥2% for blood and buccal specimens and ≥3% for saliva. When the mother’s sample is included in a Duo or Trio, it is used as a comparator during mitochondrial analysis. Mitochondrial results are included on a single consolidated report alongside the nuclear exome findings.
Is a separate Chromosomal Microarray (CMA) still needed when ordering WES+?
In many cases, a separate CMA is no longer indicated. WES+ includes a Digital Karyotype feature that uses SNP-tiling across the full genome to detect copy number variations and microdeletions with clinical utility comparable to a traditional CMA. Exon-level CNV detection is also included and detects the majority of CNVs spanning three or more exons. Clinical judgment should be applied based on the specific case.
What are secondary findings and how do I access them?
Secondary findings are results from your WES+ exome data that are unrelated to your original reason for testing. To receive them, your ordering provider can place one no-cost Hereditary Actionable Disorders (HADS) panel order within 90 days of your WES+ report release.

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Whole Exome Sequencing — Helix