FAQs

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.
The Rady Children’s Institute for Genomic Medicine-Clinical Genome Center (RCIGM-CGC) uses a symptom-driven diagnostic approach, focusing on variants classified as pathogenic (P) or likely pathogenic (LP) per ACMG guidelines that overlap with a patient’s phenotype. Selected variants of uncertain significance (VUS) are reported in accordance with RCIGM-CGC policy. 
 
Incidental findings will also be reported if identified and if the family opts-in to receive these results.
 

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:

A VUS is a variant that lacks sufficient evidence to allow for diagnosis of genetic disease due to limited or conflicting evidence of pathogenicity

A VUS may be reported in primary finding table or in a separate VUS table based on current gene-disease evidence.

RCIGM-CGC will report out a VUS when one or more of the following criteria are met:

  • VUS(s) in a gene that strongly overlaps phenotype and the mode of inheritance matches what is known about the gene of interest
  • VUS has been detected in trans (i.e., on the other allele) with a P or LP variant in an autosomal recessive condition
  • A compelling VUS(s) within a Gene of Uncertain Significance (GUS)
  • Variant must have supporting evidence of pathogenicity
    • What is known about gene function must be plausible for the pathophysiology of the condition.
  • RCIGM will not report variants of uncertain significance that are unrelated to the patient's phenotype or are weak/leaning LB.

The policy for reporting Incidental Findings is as follows:

We do not run a separate pipeline to interrogate the ACMG 59 genes. However, should a pathogenic variant in one of the ACMG 59 genes be revealed during genomic analysis for proband, and parents opt in to receive incidental findings, it will be added to the proband's report. Each parent will have the option to receive or not to receive this information for her/himself, if they opt in for proband.

If a pathogenic variant in a gene unrelated to phenotype is revealed, and that gene is not included on the ACMG 59 list, it will be evaluated by our interpretation and clinical teams for reporting. If the variant is classified as pathogenic per ACMG guidelines, is in alignment with the known inheritance pattern for the genetic condition, associated with a well established gene-disease relationship, and medically actionable, it meets criteria as an incidental finding. The finding will be included on the proband's report if parents opt in. Each parent will have the option to receive or not to receive this information for her/himself if they opt in for proband. Approximately 2% of patients sequenced in our laboratory are found to have an incidental finding.

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
  1. Complete RCIGM Phenotype Form
  2. 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.

Result turnaround time (TAT) is defined as the period from when the test is accessioned until results are signed out and reported. Our current TAT for WGS offerings are:
  • Ultra-rapid: ≤ 3 days (to provisional positive report; final written report < 14 days)
  • Rapid: ≤ 5 days (to provisional positive report; final written report < 14 days)
  • Standard: ≤ 30 days
Turnaround times may be impacted by delays in receipt of parental samples or delay in receipt of clinical records.

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
Partner PortalYou will need to authenticate via RCHSD's Microsoft 365 authentication system.
Partner account required.
or by contacting us directly at: (858) 966-8127 or RCIGM_rWGS@rchsd.org. Parents/Patients must contact the clinician who ordered testing.
RCIGM offers two types of genomic reanalysis. Keep in mind, when RCIGM analyzes cases, we perform phenotypic-driven AND phenotype-agnostic analyses looking for novel variants and novel gene-disease associations. Because of this, re-analysis requests have a low diagnostic yield of less than 5%. We continue to try and improve and automate our re-analysis efforts. Read our publication on these efforts (doi: 10.1038/s41525-020-00140-1).
 
  1. Comprehensive Reanalysis: RCIGM offers one complimentary Comprehensive Reanalysis of genomic data to the original ordering site after six months have passed from the initial analysis. This increases the likelihood that new gene-disease relationships have been reported in the literature. Comprehensive reanalysis has an average turnaround time of 4-6 weeks.
  2. Targeted reanalysis: Targeted reanalysis of genomic sequencing data may be requested for up to 50 genes.The gene list may be submitted on an Excel sheet or Word Document.If you would like our laboratory to review more than 50 genes, we would encourage completing the Comprehensive Reanalysis Form.
Additional reanalyses may be performed as a billed service. 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.

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

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