ACE Clinical Exome™ Test

Enhance Your Diagnostic Yield

The most advanced diagnostic test for inherited disease

Clinical 2016-12-03T06:23:56+00:00

The Enhanced ACE Clinical Exome™ Test

Sequencing of >20,000 genes plus augmented coverage of >8,000 medically associated genes with >6,000 of these finished*

RPGR Coverage Detail

Example of a pathogenic variant found by the ACE Clinical Exome Test that would have been missed by standard exome.

ACE Clinical Exome Test is a Next–Generation Sequencing (NGS)-based test designed to provide a molecular genetic diagnosis for patients whose clinical assessment indicates a likely genetic basis to their disorder but that genetic etiology is unknown. The ACE Clinical Exome Test “finishes” over 6,000 clinically important genes, covering > 99% of all exonic bases at an average depth of ≥ 20x, a depth sufficient to call heterozygous variants with confidence. It is based on the ACE Platform, ensuring high accuracy sequencing, variant calling, and interpretation for enhanced diagnostic yield.

* > 99% of exonic bases at ≥ 20x coverage

Enhanced coverage of over 8,000 genes of clinical importance
Clinically interpretable non-exonic content
World-class clinical interpretation and medical review

What is Exome Sequencing?

The human exome is the complete collection of regions of the genome that encode protein i.e., all the protein-coding exons of all the protein-coding genes. These regions of the genome are the best understood and therefore the most biomedically interpretable.

Whole exome sequencing is the process of selecting and then sequencing these regions of the genome using NGS technology. A whole exome sequencing test therefore involves sequencing the patient’s exome in a single test with the aim of arriving at a diagnosis, rather than choosing individual genes to sequence. Exome sequencing offers potential advantages over traditional genetic testing by reducing costs and time to diagnosis, and making difficult molecular diagnoses possible.

When to Order the ACE Clinical Exome Test

Exome sequencing is an appropriate test for individuals with a condition that is suspected to be caused by a variant(s) in a single gene (i.e., a Mendelian condition). The American College of Medical Genetics issued a policy statement outlining the following indications for diagnostic testing via exome/genome sequencing:

  1. The etiology of the patient’s disorder is likely genetic but no specific genetic test is clinically available for the disorder in question.
  2. The genetic disorder in question demonstrates a high degree of genetic heterogeneity, i.e., there are many genes that cause a patient’s condition and it may be inefficient both in terms of time and cost to sequence them all individually.
  3. The etiology of the patient’s disorder is likely genetic and the patient has had genetic testing for their disorder but this has not provided a diagnosis.

Genet Med. 2012 Aug;14(8):759-61

Exome Sequencing Consultation

If you would like assistance in determining if the ACE Clinical Exome Test is appropriate for your patient, you may contact us by by calling 650-752-1349, or by emailing us at clinical@personalis.com.  Please use a secure email system if transmitting any protected health information (PHI).

How Does the ACE Clinical Exome Test Compare with Conventional Exome Sequencing Tests?

Unlike other exome sequencing platforms, the ACE Clinical Exome has been specifically designed to enhance diagnostic yield for clinical care. The ACE Clinical Exome has several major features that are not addressed by standard exome sequencing platforms: a high level of gene finishing, and inclusion of non-exonic interpretable content.

Gene Finishing
While standard exome sequencing platforms attempt to capture the protein-coding regions of the genome, they routinely exhibit incomplete coverage of biomedically important genes. In contrast, single gene tests/gene panel tests generally involve sequencing all of the coding bases of a gene, as well as the intron-exon boundaries. The ACE Clinical Exome Test was designed with the aim of “finishing” the biomedically interpretable genes in the exome to a similar standard as single gene sequencing. As a result, the ACE Clinical Exome Test provides the highest available level of biomedical gene coverage in an exome platform, increasing sensitivity to detect potentially pathogenic variants in these genes.
Non-exonic Interpretable Content
While the majority of known pathogenic variants reside within the coding regions of genes, there are many well-characterized pathogenic variants located in introns, UTRs, promoters, etc. The presence of such non-exonic variants is not generally detected using standard exome platforms since only exonic content is captured and sequenced. The ACE Clinical Exome Test has been designed to include these biomedically relevant variants.

ACE Clinical Exome Test Comparison to Other Technologies

Single Gene / Gene Panel Tests Conventional Exome Test ACE Clinical Exome™ Test
High levels of gene finishing for clinically important genes ACE Clinical Exome Comparison ACE Clinical Exome Comparison ACE Clinical Exome Comparison
Exome-wide sequence coverage ACE Clinical Exome Comparison ACE Clinical Exome Comparison ACE Clinical Exome Comparison
Detection of non-coding clinical variants ACE Clinical Exome Comparison ACE Clinical Exome Comparison ACE Clinical Exome Comparison
ACE Clinical Exome Comparison Provided by some tests
*The ACE Clinical Exome Test should be considered as described under the “When to Order an ACE Clinical Exome Test” section (above) and should be used in conjunction with other tests (such as, and not limited to, cytogenomic microarrays and targeted single gene/gene panel sequencing).

Regulatory

The ACMG Guidelines for Molecular Genetic Testing for Ultra Rare Disorders states: “Under state and federal regulations, only licensed clinical laboratories are legally permitted to perform testing on patients in which the results are released directly to patients or their physicians and used for medical management.” Personalis’ laboratory is CLIA-certified and CAP-accredited.

CLIA and CAP