Rapid and Ultra-Rapid whole genome sequencing (rWGS^®) must be ordered by a clinician who is licensed to order genetic testing.

rWGS^® is best considered for critically-ill infants and children in the inpatient setting for which a rapid genetic diagnosis could impact medical management and outcomes.

Indications for rWGS^® testing include:

• Critically-ill infants and children in the intensive care unit with no unifying diagnosis
• Critically-ill infants and children for whom a rapid molecular diagnosis may inform medical management, treatment and/or prognosis
• Molecular diagnosis of suspected genetic disease
• Identification of rare genetic disease variants in patients who have failed to receive a diagnosis despite extensive work-up and previous testing
• Infants and children with a history of multiple hospitalizations or readmission within 30 days of discharge for an unexplained condition
• Infants or children with prolonged hospital stay

Considerations for Ultra-Rapid WGS include, but are not limited to, the following:

• Primary admission for intractable seizures
• Suspected inborn error of metabolism including profound hypoglycemia
• Unexplained cardiac arrest
• Invasive diagnostic procedures or heroic measures being considered during current hospitalization that may be avoided based on UR-WGS results (e.g., muscle or liver biopsy, ECMO, surgery)
• BRUE with concern for more serious course or other features such as seizures or family history of long QT, sudden death or SIDS that leads to inpatient observation
• Other condition for which a delayed diagnosis has a high likelihood of adverse effects (due to inappropriate therapy) or severe morbidity or mortality (due to delayed specific treatment) that is not one of the noted exclusion indications

• Please call (858) 966-8127 if inquiry is taking place Monday-Friday 9am-5 pm PT.
• For after hours or weekend inquiries, please call (858) 900-5979.

If a child’s clinical course is entirely explained by 1 or more of the following, they are unlikely to benefit from Rapid or Ultra-rapid WGS:

• Infection or sepsis with normal response to therapy
• Isolated prematurity
• Isolated unconjugated hyperbilirubinemia
• Hypoxic ischemic encephalopathy with clear precipitating event
• Previously confirmed genetic diagnosis that explains their clinical condition (i.e. have a positive genetic test)
• Isolated transient neonatal tachypnea
• Trauma
• Meconium aspiration

It is recommended that samples from biological parents be sent whenever they are available, but they are not required for RCIGM-CGC to perform genomic analysis. Even when ordering Proband-only rWGS, we request that you send parental samples which may inform variant classification/phasing and inheritance.

Ultra-rapid WGS is best performed when a biological trio is sequenced concurrently, but may be performed with duos or singletons. Please note that RCIGM-CGC’s commitment to provisional time reporting does require trios. Whole blood is required for this testing.

Whenever possible, please send parental samples along with patient’s, but do not delay in sending patient samples. If parents are not immediately available, their samples can be sent in a subsequent shipment.

RCIGM-Clinical Genome Center is validated to report on the following:

• Single nucleotide variants (>99.8% sensitivity)
• Small insertions or deletions (reported up to 40 bp)
• Small copy number variation (down to 1 kb)
• Large copy number variation (microdeletion/microduplication syndromes)
• Aneuploidy (whole chromosome)
• SMN1/SMN2 copy number analysis (0,1,2, and > 3 copies)
• Mitochondrial DNA (variants (down to 1% heteroplasmy) Download our Test Specifications.

Refer to our gene coverage tool here (downloadable searchable Excel file).

Benign and Likely Benign variants are not reported. In addition, RCIGM-CGC does not report on carrier status, pharmacogenetic markers, polygenic risk scores, or genome wide association studies (GWAS) risk variants.

Also not reported: variants of uncertain significance that are unrelated to the patient's phenotype or are weak/leaning LB.

Selected Variants of Uncertain Significance will be reported according to RCIGM-CGC Policy:

RCIGM does report incidental findings (if proband is opted in to receive them), but RCIGM does not report secondary findings (see definitions below).

Incidental Findings: variants that are incidentally ascertained during genomic analysis and do not overlap with the proband's reported phenotype.

Secondary Findings: variants identified during a separate, intentional analysis for a selected list of genes such as the ACMG Secondary Findings list.

RCIGM does not run a separate pipeline to interrogate incidental findings or the ACMG secondary findings gene list. However, should a variant be revealed during genomic analysis in the proband that meets the RCIGM incidental findings criteria below, that variant will be reported as an incidental finding on the final report.

RCIGM Incidental Findings Policy:

Incidental findings are only reported when the proband is opted in to receive incidental findings. If the proband is opted in to receive incidental findings, then each parent will have the option to receive or not receive this information for themselves. If the parents opt in to receive incidental findings, then any incidental finding reported in the proband will include parental inheritance on the final report. RCIGM will not report incidental findings if the proband opted out of receiving them, even if parents opted in. Approximately 2% of patients sequenced in our laboratory are found to have an incidental finding.

Incidental findings are reported when the following criteria are met:

1. Proband is opted in to receiving incidental findings.
2. The variant is classified as pathogenic or likely pathogenic (note: classification requirements vary by gene).
3. The detected variant(s) are in alignment with the known inheritance pattern of the genetic condition (note: gene-disease relationship must be well-established).
4. The gene and associated condition are shown to be medically actionable as established by RCIGM policy or the gene falls within the ACMG list of secondary findings genes.

Please see the How to Order page.

The Test Requisition form is available in our Clinician Toolbox.

Send relevant clinical notes, by one of four options:

• Upload to
  
  RCIGM Ordering PortalYou will need to authenticate via RCHSD's Microsoft 365 authentication system.
  Partner account required.

  with case order (preferred option).

• Encrypted/secure email: RCIGM_rWGS@rchsd.org
• Include them in the package containing the sample and Test Requisition form.
• Fax to (858) 966-8092

Clinical notes from the EMR, including:

• • Recent progress notes from NICU/PICU
  • Medical genetics/genetic counseling notes (including pedigrees)
  • Consult notes from specialists. (e.g. cardiology, neurology, gastroenterology, immunology, etc.)
  • Results or status of other genetic tests ordered (e.g. chromosomal microarray, gene panel, single gene testing, etc.)
  • Laboratory results (e.g. hematology, biochemical, immunology)
  • Imaging (echocardiograms, EEGs, skeletal surveys)
  • Differential diagnosis

At present, our laboratory is validated to run whole genome sequencing on whole blood or DNA isolated from whole blood when collected in an EDTA tube. Saliva specimens may be used for phasing, classification, or inheritance of variants for informing proband’s WGS testing or for custom variant analysis testing.

See the full Specimen Requirements on the How to Order page.

Please contact RCIGM_rWGS@rchsd.org for information about specimen collection kits.

Send specimens to:

Rady Children’s Institute for Genomic Medicine
7910 Frost St, Suite 240
San Diego, CA 92123
Attn: Clinical Genome Center

See How to Order for detailed Shipping Instructions.

Clinicians may check the case status on the

or by contacting us directly at: (858) 966-8127 or RCIGM_rWGS@rchsd.org.

Parents/Patients must contact the clinician who ordered testing.

Yes. Rady Children’s Institute for Genomic Medicine offers one complimentary reanalysis of genomic data to the original ordering site. Additional reanalyses may be performed as a billed service. We recommend waiting six months before ordering a reanalysis to increase the likelihood that new gene‑disease relationships have been reported in research literature.

Our WGS testing provides both phenotypic-driven and phenotypic-agnostic analysis and RCIGM lab directors and analytical staff are looking for novel variants and novel gene-disease associations during each analysis.

Please contact us with questions or reanalysis requests at RCIGM_rWGS@rchsd.org.

Clinicians may call (858) 966-8127 if inquiry is taking place Monday-Friday 9am-5pm PT.

After hours or weekend inquiries, call (858) 900-5979.

If you have questions regarding data, record, or sample transfers please contact RCIGM_rWGS@rchsd.org.

Please email ask@RadyGenomics.org and a member of our Business Development team will reach out to you promptly.