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PGxomeTM-Based Tests Validated for Copy Number Variants

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PGxomeTM-Based Tests Validated for Copy Number Variants

We are pleased to announce that all of PreventionGenetics’ PGxomeTM (whole exome sequencing) based sequencing tests are now validated for copy number variant (CNV) detection.  In many cases, this will alleviate the need for chromosomal microarray (CMA) or gene-centric array Comparative Genomic Hybridization(aCGH) tests, thereby increasing the value for you and your patients!

We utilize a CNV calling algorithm that compares mean read depth and distribution for each target in the patient’s specimen against multiple matched controls. Neighboring target read depth and distribution as well as zygosity of any variants within each target region are used to reinforce CNV calls. 

All CNVs are confirmed using another technology such as aCGH, MLPA, or PCR before they are reported.


For PGxomeTM, we will generally only report CNVs of 4 or more exons in size unless a smaller CNV is consistent with the clinical indication (specifically, the second pathogenic finding for a recessive disorder) or is within one of the ACMG recommended secondary finding genes. CNVs will not typically be assessed solely for carrier status or other secondary findings.

PGxomeTM Custom Panels

PreventionGenetics strives to be fully transparent with regards to our testing methodologies.   We believe the ability to detect CNVs will greatly increase the value of our PGxomeTM-based tests. However, given the complexity of the genome, there are limitations to these tests.  In general, sensitivity for single, double, or triple exon CNVs is ~70%. Sensitivity for CNVs in size of four exons or larger is >95%. These detection rates may vary from gene-to-gene based on exon size, depth of coverage, and characteristics of the region. Balanced translocations or inversions within a targeted gene are generally not detected. The  ability to detect CNVs due to somatic mosaicism is limited. Aberrations in a small percentage of regions may not be accurately detected due to sequence paralogy (e.g., pseudogenes, segmental duplications), sequence properties, deletion/duplication size, and inadequate coverage.

Role for Gene-Centric aCGH

Where desired, del/dup testing is available also via gene-centric aCGH for nearly 1500 genes on our menu. PreventionGenetics' high density gene-centric aCGH is designed to have comprehensive coverage for coding regions (18 bp median probe spacing) and non-coding regions (87 bp median probe spacing) for each targeted gene and includes coverage of all transcripts. We also include probe coverage 5kb upstream and downstream. In addition, the flanking 300-bp intronic sequence on either side of targeted exons has enriched probe coverage. Array Comparative Genomic Hybridization enables the detection of deletions and duplications of single and multiple exons within a given gene as well as full gene deletions or duplications (Tayeh et al. 2009). At this time, sensitivity for smaller CNVs (1-3 exons) is still generally superior to CNV detection through sequencing. This test involves analysis only of the specific gene(s) of interest for each patient. Gene-centric aCGH can be ordered via Test Code 600 for genes that are available. This test can be performed concurrently or as a reflex from sequencing.

Upcoming Changes

PreventionGenetics currently offers two types of panels: PG-Select and PGxomeTM-based panels. Our PG-Select panels are generally smaller panels and mostly do not include CNV detection with sequencing. Gene-centric aCGH is available for many of the genes on our PG-Select panels. Over the coming weeks and months, many of our PG-Select panels will be moving to PGxomeTM-based panels, thus allowing for the inclusion of CNV detection! Please see the methods section of individual test descriptions for coverage details. Check our website regularly for potential updates on your frequently ordered panels.