Enhanced Whole Exome Sequencing

The Enhanced Exome test is a clinical diagnostic genetic test designed to identify pathogenic variants through whole genome sequence analysis.

By using a whole genome sequencing platform methodology in conjunction with the Variantyx Genomic Intelligence® interpretation software, many more variants can be evaluated than is possible with standard exome tests. The Enhanced Exome test includes small sequence changes (single nucleotide variants), small insertions and deletions (delins), short tandem repeats (STRs), mitochondrial genome single nucleotide variants and deletions/duplications (del/dups).

Standard targeted whole exome sequencing methods generally detect single nucleotide variants and small insertions or deletions of less than 50 bp in exons and identifies a disease-causing variant in up to half of cases predicted to be genetic in origin leaving many cases unsolved.

Whole genome sequencing includes variants detected in whole exome sequencing but adds the ability to uncover additional types of variants. These include pathogenic single nucleotide variants found in regions outside the exome. Whole genome sequencing can also identify structural variants and copy number variations of entire exons, genes or large chromosomal duplications or deletions traditionally identified by chromosomal microarray hybridization.

Many rare diseases are caused by nucleotide repeat expansions that are detectable by WGS.

Previously, these tests were ordered individually and reports issued separately such that complex inherited diseases containing multiple variant types were not considered together and a diagnosis would more likely be missed.

We have partnered with VariantYX and utilize their Genomic Intelligence clinical interpretation software to combine all these types of genetic analysis into a single test.

This test is able to detect exonic single nucleotide variants, small insertions and deletions, known pathogenic intronic single nucleotide variants, copy number and structural variants and many repeat expansions all in a single test thus allowing diagnosis of complex diseases. This WGS assay also detects mitochondrial single nucleotide variants at heteroplasmy of >5%. The ability to screen for multiple variant types simultaneously should significantly decrease the diagnostic odyssey for those patients who must currently wait for tests to be performed sequentially.

Key Features

The most comprehensive variant detection available

✓ Single Nucleotide Variants (SNVs)

✓ Short tandem repeat expansions (STR)s

✓ Structural variants (≥ 50bp) – Copy Number Variants (CNVs) and Deletion/Duplications (del/dups)

✓ Small Deletions/Insertions (delins (< 50bp))

✓ Mitochondrial SNVs (≥ 5% heteroplasmy)

  • Exonic, intronic and regulatory region SNV and small insertions and deletions <50 bp.
  • Genome-wide deletion and duplication analysis
  • Short tandem repeat detection for: AFF2, AFF3, ATN1, ATXN1, ATXN2, ATXN3, ATXN7, ATXN8OS, ATXN10, c9orf72, CACNA1A, CNBP, CSTB, DIP2B, DMPK, FMR1, FXN, PP2R2B, with optional inclusion of HTT and JPH3
  • Mitochondrial analysis of SNV and small insertions and deletions <50 bp to 5% heteroplasmy
  • High coverage of exonic variants
    • WGS provides a consistent read depth, reducing the likelihood for missed exonic variant calls
  • Detection of additional variant types
    • Consistent read depth also allows for the detection of small sequence changes, structural variants, tandem repeat expansions, and mitochondrial variants, all within a single test.

Test Characteristics

Clinical-grade whole genome sequencing is conducted on an Illumina platform using the Illumina TruSeq DNA PCR-Free Library Preparation Kit.

  • Highly uniform sequencing depth
    • 30X mean mappable coverage
    • 97.3% of nucleotides covered at ≥8x
    • 99.4% of HGMD and ClinVar annotated variants covered at ≥8x
  • Highly sensitive and specific detection of SNVs and indels up to 50 nucleotides
    • 99.9% sensitivity
    • 99.9% specificity
    • 99.6% positive predictive value for SNVs
    • >95% sensitivity for indels
  • Highly sensitive detection of structural variants
    • 96% clinical sensitivity for structural variants
    • In most cases, the exact genomic coordinates of the structural variant can be determined
  • Sensitive detection of tandem repeat allele counts for >20 known pathogenic loci
  • Trios are encouraged but not required.
  • Analysis software provided by Variantyx Genomic Intelligence software.

Data Reporting

  • Reported findings are those that are directly related to the reason(s) for testing the patient, or that fall within genes evaluated for their association with the reason(s) for testing.  Secondary findings are only provided for the patient when specifically opted in. Secondary findings are limited to the set of 59 genes recommended by the American College of Medical Geneticists for WES and WGS reporting. Only pathogenic and/or likely pathogenic secondary findings are reported.
  • Because WGS covers an individual’s entire genome it is not biased by current knowledge of disease-variant or disease-gene associations. WGS results can easily be reanalyzed as more information becomes available, or as variant calling algorithms become even more sophisticated.
  • Reanalysis offered once within the first 24 months for no charge.

Turn Around Time 8-10 weeks

How To Order