Whole Genome Sequencing (WGS) Enhancements and RNA Sequencing Ordering Updates for WGS and Whole Exome Sequencing

Effective March 24, 2026, the following enhancements will be added to Baylor Genetics’ Whole Genome Sequencing (WGS) and Whole Exome Sequencing (WES) products.

WGS Enhancements

All new WGS orders, as well as pending WGS orders that have not yet been reported, will be eligible for expanded WGS analysis supported by optical genome mapping (OGM) and long-read sequencing (LRS).

This expanded analysis includes the following additional enhancements:

• Enhanced short tandem repeat (STR) analysis, increasing coverage from 29 to 58 genes with STRs associated with neurological, neuromuscular, and other conditions.
• Methylation analysis to detect FMR1 methylation status associated with Fragile X syndrome.
• Complex structural variant (SV) analysis to augment detection and improve interpretation of potential findings identified through standard WGS.

Impacted WGS Test Codes

RNA Sequencing Ordering Update

Additionally, RNA Sequencing (RNA-Seq) will be automatically included with every WGS proband sample when a qualifying variant is identified.¹ RNA-Seq analysis will no longer be available as an opt-in or opt-out option, ensuring eligible cases consistently benefit from more confident variant interpretation.

Newly Added STR Genes²

The (STR) analysis has been expanded to deliver broader, clinically meaningful insights. Coverage now increases from 29 to 58 genes.

To see Baylor Genetics’ full list of STRs and associated conditions, download the latest WGS booklet and refer to page 13.

Methylation Analysis

For Fragile X syndrome assessment, LRS will be used for male patients with approximately 150–200 CGG repeats and female patients with over 150 CGG repeats to clarify methylation and disease status.

Validated Specimens

Samples collected from WGS may be used for additional analysis. Additional specimens may be requested as needed. Please note that this requisition replaces the previous RNA Sequencing Requisition form.

The Additional Testing Requisition form can be found here.

Validated Specimen Types for Updated Testing Modalities

Turnaround Time and Report Delivery Expectations

For select cases, when deemed appropriate by Baylor Genetics, WGS may be supplemented by RNA-Seq and/or OGM to aid with variant classification and clarifying results as a standard part of WGS testing.

If the original submitted specimen is blood and meets all established specimen requirements, RNA-Seq and/or OGM will be reflexively performed without additional authorization. If these requirements are not met, submission of a new blood specimen may be requested, or reflexive testing may not be performed.

A final report will be issued before RNA-Seq and/or OGM is initiated. Any updates from these additional technologies will be provided in an addended report, issued within 28 days of the initial final report or receipt of a new specimen, if applicable.

For rapid cases and other situations requiring supplementary or confirmatory testing, turnaround time (TAT) may extend beyond the standard quoted timeframe. Identified STR expansions and results from FMR1 methylation analysis will be included in the final report within the standard TAT whenever possible. Otherwise, results will be issued once analysis is complete.

New York State Approval

Samples collected from New York State (NYS) are approved for WGS, along with RNA-Seq. However, the additional technologies incorporated into Baylor Genetics’ WGS platform, which include OGM and LRS, are not currently approved by NYS. Specimens collected in NYS cannot be reflexed to these technologies.

Baylor Genetics is not offering any exemptions at this time, and affected physicians will be notified when NYS approval is granted.

WES Enhancements

RNA-Seq Ordering Update

RNA-Seq will be automatically included with every WES proband sample when a qualifying variant is identified.¹ RNA-Seq analysis will no longer be available as an opt-in or opt-out option, ensuring eligible cases consistently benefit from more confident variant interpretation.

Impacted WES Test Codes

Baylor Genetics is committed to advancing rare disease diagnostics through these new technologies and enhancements. Providers can learn more by visiting Baylor Genetics’ WGS enhancements page.

For questions about these changes, your Baylor Genetics regional account executive is ready to help. You may also contact Client Services at 1-800-411-4363 or [email protected].

Thank you for your continued partnership and for the care you provide to patients and families every day.

Disclaimers:

1. 1. RNA-Seq is only performed on qualified variants that meet the prediction algorithm criteria that suggest additional functional evidence can be provided. RNA-Seq is only available for the proband sample, including when ordered with comparators (i.e., duo, trio, quad).
   2. STR analysis is confirmed by LRS and other methods