A patient’s clinical presentation may change and evolve over time, as does our understanding of the genetics underlying hereditary disease. For these reasons, Blueprint Genetics offers:
- A WES Variant Re-evaluation service in an attempt to re-classify variants originally classified as a variant of uncertain significance (VUS) or as Likely Pathogenic (LP).
- A more comprehensive WES Re-analysis Service, allowing the sequencing data from a previous exome to be re-analyzed, in its entirety, to look for new clinically relevant variants that may explain or contribute to your patient’s diagnosis.
Blueprint Genetics WES Variant Re-evaluation Service
Blueprint Genetics provides a WES variant re-evaluation service that:
- Revisits reported VUS and LP variants from a previous WES order. Re-evaluation is done only for those variants that have been described in the clinical report.
- Can be requested between 12 to 24 months after the original results are reported
- Might change the classification of previously identified variants based on advances in scientific knowledge made between the time of reporting and the time of re-evaluation
How to order:
1) Contact firstname.lastname@example.org via email requesting WES re-evaluation and include the Order ID (more detailed contact information for Support below)
2) Indicate the variant(s) you want re-evaluated
3) Include up-to-date clinical and/or family history information. Alternatively, indicate if there is no change. A detailed description of the patient’s phenotype gives us the best chance for reclassification of the variant in question. Note: do not include any identifiable information about your patient
4) Once we have received the request for variant re-evaluation and updated clinical information, the turnaround time is 28 working days
5) Once the re-evaluation is complete, an updated report will be available in Nucleus
What does the WES Variant Re-evaluation involve?
Upon request, we will review the relevant literature, available variant databases, and the latest research for new classifications or information regarding the previously reported VUS or LP variant in question and evaluate whether the new evidence will impact the original variant classification.
Which variants are eligible for re-evaluation under the WES Variant Re-evaluation service?
Variants reported as primary findings with a classification of VUS or LP are eligible for the WES Variant Re-evaluation service. Re-evaluation is done only for those variants that have been described in the primary findings section of the clinical report.
What is involved in variant re-classification?
Our interpretation team analyzes millions of variants from thousands of individuals with rare diseases. Our database, and our understanding of variants and related phenotypes, continues to grow by leaps and bounds. Our laboratory is well positioned to re-classify previously reported variants as new information becomes available.
In the event that we do re-classify a VUS or LP relevant for one of your patients while evaluating the same variant in another patient, our laboratory will automatically provide you with an updated result.
Blueprint Genetics WES Re-analysis Service
WES Re-analysis Service allows the patient’s sample to be re-sequenced or the sequencing data from a previous exome to be re-analyzed in its entirety. The goal is to find new clinically relevant variants that may explain or contribute to your patient’s diagnosis.
What is involved in the WES Re-analysis service?
- The patient’s sample is either re-sequenced or raw data from a previously ordered exome are re-entered into our bioinformatics pipeline
- A new report is provided, including full interpretation of any newly identified variants and updated classifications of previously identified variants where applicable
- All WES Re-analysis requests will be analyzed as WES, which includes sequencing and deletion/duplication analysis (or WES Family, if the initial order was a WES Family order).
- A new report will be issued and will be available on our online portal, Nucleus. Faxed or land mailed copies are available upon request.
- The turnaround time of the WES Re-analysis Service is 8 to 10 weeks.
- Secondary findings can be included upon request, if the patient was consented either at the time of the preliminary order or during the re-analysis order
- If the patient opted-in for secondary findings with the primary order then the secondary findings will always be reported during re-analysis and no new consent is needed
- If the patient had not consented to receiving secondary findings OR if no consent form was provided at the time of the preliminary analysis, but the patient now wishes to receive secondary findings during exome re-analysis, a consent form must be received
- If no consent form is received, secondary findings will not be reported as all patients must opt-in to receiving secondary findings.
When can I request the WES Re-analysis Service?
- We will accept requests for WES Re-analysis any time between 12-24 months after the original results were reported.
- Waiting at least 12 months between reporting and re-analysis allows the best chance for the maturation of scientific knowledge
- Requests made less than 12 months after the original results are reported will be performed if there is a significant change to the patient’s phenotype or the clinician provides new scientific information to support the re-analysis.
What is the diagnostic yield of WES re-analysis?
The diagnostic yield of exome reanalysis varies but is often estimated to be between 5 to 15%. However, this estimate is highly dependent upon the technology and interpretation strategy used during the first analysis. At Blueprint Genetics, our WES is analyzed using a genotype-first approach which means that we look at all likely disease-causing variants identified by our pipeline to see if the variant and gene offer an explanation for all, or part, of the patient’s phenotype.
The genotype first approach allows for the identification of atypical presentations of known disorders, expansion of phenotypes, diagnoses in newly established genes and reporting of variants in promising candidate genes.
Given Blueprint Genetics interpretation strategy, a minor change in the patient’s phenotype is unlikely to change our interpretation of the identified variants. However, a significant change in the patient phenotype or clinical information (for example, symptoms in a new body system, new family history, etc) may result in new variants being reported or updated classifications for existing variants.
How do I request a WES Re-analysis?
- Send your request to our Customer Support team by email (email@example.com)
- Please do not include any patient identifying information in your email.
- the previous Order ID, patient’s initials and DOB.
- a brief description of all new clinical information (updated phenotypic information).
- If you, or another health care provider at the same institution, did not order the original WES, a signed PHI release form is required.
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