What are the benefits of a genetic diagnosis?
• Your patients might avoid additional testing.
• The test might indicate treatment
• The test may change the way you survey the patient in the future
• Help patient with their life and financial planning
• Recurrence risk factors can be discussed
• Your patient might have an answer and can stop asking “Why”
Each person’s DNA is a unique blueprint that provides the building blocks for human life. While this genomic blueprint does not define every aspect of our lives, access to personal genome information and an understanding of how that information could be used to benefit healthcare or mitigate disease risk is of great interest to many people. For some, genome sequencing information will be impactful in the management of disease or risk for disease or the determination of carrier status for use in family planning.
Who benefits from clinical genome sequencing?
Testing is useful for patients with rare inherited disorders or with complex clinical presentations lacking a clear diagnosis.
Ideally, sequencing can contribute to a diagnosis, potentially getting answers that have been elusive. The medical provider can then use that diagnosis to avoid additional tests and develop a treatment plan. Sequencing and analysis could also shed light on recurrence risk factors and assist with family planning.
Patients under consideration should be evaluated by medical providers with expertise in the patient’s condition to help the laboratory correlate patient symptoms and family history with the variants identified from sequencing. The provider should consider patients with an undiagnosed disorder with a suspected genetic cause. Patients with rare or distinctive symptoms or a strong family history with multiple affected members may derive the most benefit.
What do patients need to know about genetic sequencing?
Clinical tests must be ordered by a licensed health care provider, physician assistant, or nurse practitioner. Consider directing patients to the Smith Family Clinic’s Frequently Asked Questions for more information. The Smith Family Clinic for Genomic Medicine, LLC is located on the HudsonAlpha Institute for Biotechnology campus and works with the Clinical Services Lab for clinical genomic sequencing. You might also consider directing patients to the clinic’s fundamental information on genetic sequencing or Our genetic counselors have put this slideshow together to help you discuss genetic information with your patient: Genomics and Your Patients.
Is there a danger of having a genome sequenced?
Sequencing provides information about DNA and variants within. It does not change DNA or directly increase or decrease the risk of disease. It may reveal surprising information about ancestry or family history. It could also reveal a risk for a disease or a condition where there is no possible treatment. Each person will have their own thoughts and opinions on how this type of information may impact them or their family and therefore should carefully consider the potential positive and negative aspects of knowing your genetic makeup. The most important consideration is that no one can provide all of the answers today. It is recommended that genetic counselors be involved in a patient’s decision to have genomic sequencing performed, and also to assist in the interpretation and meaning of results.
What do physicians need to know about whole genome sequencing?
This test is designed to determine the entire genetic makeup of an individual by sequencing, or reading, the entire genome. Six billion data points are sequenced and evaluated to identify variants of interest in disease diagnosis and other clinical purposes.
Whole genome sequencing identifies several million variants in an individual that differ from the reference genome. Most of these variants are benign (having no effect on health), but a small number of variants are pathogenic (related to disease). There are also many rare variants whose relationship to disease is not well understood at this time, which are referred to as variants of uncertain clinical significance. As the field of genomics matures it is likely that our knowledge of these variants will improve.
The ability to interpret the significance of a rare change in a gene depends on how well the function of that gene is understood. Currently, some genes are well understood, while others have not been as well studied. At present, about a quarter of genes have been connected to human disease. That number continues to rise as scientists connect other genes to disease.
How does the CSL handle data and privacy?
The lab is HIPAA compliant, and the reports are only released to the ordering physician or other entities that are specified by the patient. The Clinical Services Lab, LLC recognizes that patients own their data and can request it at any time. The CSL does not sell sequencing data to third parties. For more information on data and sample storage, contact the CSL.
What are the specimen requirements?
Blood or DNA samples may be submitted for analysis for whole genome sequencing.
Blood Sample Requirements
- Collect 2-4 ml of whole blood in EDTA (lavender top) tube. 2 EDTA tubes containing 2-4 ml of whole blood per patient preferred.
- For infants, collect a minimum of 1 ml of blood.
- Label the specimen with at least two identifiers; patient name and date of birth are preferred.
- Ship blood in tubes at room temperature in an insulated container.
- The specimen should be submitted within 48 hours of collection. Every attempt will be made to process samples older than 48 hours.
Possible reason for sample rejection:
Coagulated sample, quantity less than one ml, specimen collected in wrong tube or unlabeled sample.
DNA Sample Requirements
DNA Samples are ONLY accepted from CLIA-certified laboratories. You can find more information on CLIA labs here.
Required: CLIA License Number (Federal and state, if applicable)
- DNA quantitated via spectrometry. Submit a screw cap tube of at least 5ug of purified DNA at a concentration of at least 60ng/ul with a 260/280 purity ratio of 1.75 – 2.0.
- DNA quantitated via fluorometric assay (PicoGreen). Submit a screw cap tube of at least 3 ug of purified DNA at a concentration of at least 50 ng/ul
- DNA may be shipped at room temperature. Label the specimen with at least two identifiers; patient name and date of birth are preferred. To maintain clinical level testing, genomic DNA from CLIA laboratories is required. Products of whole genome amplification reactions or other amplification reactions.
Possible reason for sample rejection:
Degraded sample, sample not extracted in CLIA laboratory or low DNA concentration.
What can patients expect from a report?
A genomics report will include rare variants that are suspected to cause disease in genes that are associated with the patient’s symptoms. The patient may elect to have additional findings in the report (secondary findings) such as variants associated with later onset diseases, carrier status or pharmacogenetics.
How long will it take? Most reports are given to physicians within 45-60 days.
Under the HIPAA Privacy Rule, patients, patient’s designees and patient’s personal representatives can see or be given a copy of the patient’s protected health information, including an electronic copy, with limited exceptions. The patient or the personal representative must put their request in writing and pay for the cost of copying, mailing, or electronic media on which the information is provided. Copies will be sent to the patient within 30 days of his or her request. Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulations to allow laboratories to give a patient, or a person designated by the patient (his or her “personal representative”) access to the patient’s completed test reports on the patient’s or patient’s personal representative’s request.
How do I ship a sample?
- Please contact us at email@example.com or through our contact form to have your facility registered as a provider. Basic information as well as provider ID will be required.
- Samples may be submitted from a clinical collection lab as blood or purified DNA. For submission of blood, Beckton Dickinson ® Vacutainer EDTA Tubes are requested (lavender or pink) with lavender preferred. Also accepted is BD Vacutainer Specialty Tube (yellow). Heparin is a powerful PCR inhibitor and co-purifies with DNA. Therefore, blood collected in Heparin-coated tubes should not be submitted.
- Label samples with two unique identifiers, typically a patient’s name and date of birth.
- Package the forms, the sample and include a signed medical provider order (required for clinical sample processing). You can find the CSL’s test request form here.
- Print and sign the Hazardous Declaration Form to include with your shipment. Samples shipped without this document will be discarded.
- Pack samples as diagrammed at the side.
- Ship samples overnight to the address below. We advise shipping no later in the week than Wednesday in case a carrier delay causes samples to sit over the weekend.
- Shipping address: HudsonAlpha Clinical Services Lab, LLC, 601 Genome Way, Room 3023, Huntsville, AL 35806
How long does the process take?
The turnaround time for clinical genome sequencing with the final report ranges between 45 and 60 days. The final report includes variants in genes related to patient symptoms that may be clinically relevant and are confirmed by a different (orthogonal) method. Rapid genomes with a preliminary report between five and ten days may be available. Please contact the laboratory for details.
Generally speaking, once a genome is sequenced, there is not likely to be a strong benefit to have it sequenced again. Situations like cancer may warrant having a suspected cancer sample characterized, but once a genome is sequenced, only a substantial change in technology with drastically increased resolution would merit another whole genome assay. While the assay will typically not be performed more than once, it will be routine for physicians to reanalyze and annotate a patient. Re-analysis costs are not included in the price for whole genome sequencing through the HudsonAlpha Clinical Services Lab.
What can physicians expect to get back in the report?
For interpreted genome sequencing, a clinical report will be provided to the requesting medical provider with a list of variants identified that are relevant to a patient’s symptoms. If a patient consents, the report will also include secondary findings unrelated to symptoms and/or pharmacogenomic variants.
Upon agreement with the CSL, medical providers that perform their own interpretation will receive the relevant sequencing files (FASTQ, BAM, and/or VCF) and a report of sequencing performance metrics.
The clinical report comes in a PDF signed by the director or associate director of the Clinical Services Lab. Reports may also be faxed.
Primary findings include variants in genes related to patient symptoms that are pathogenic, likely pathogenic or of uncertain significance. Secondary findings, when requested with patient consent, include dominant disorders for childhood and adulthood, carrier status for recessive disorders and pharmacogenomic variants for CPIC level 1A/1B evidence.
Under the HIPAA Privacy Rule, patients, patients’ designees and patients’ personal representatives can see or be given a copy of the patient’s protected health information, including an electronic copy, with limited exceptions. The patient or the personal representative must put their request in writing and pay for the cost of copying, mailing, or electronic media on which the information is provided. Copies will be sent to the patient within 30 days of his or her request. Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulations to allow laboratories to give a patient, or a person designated by the patient (his or her “personal representative”) access to the patient’s completed test reports on the patient’s or patient’s personal representative’s request.
How much does sequencing and analysis from the CSL cost?
Our sequencing and analysis are offered at a competitive price for patients, grant-funded researchers, and institutions. Patients may even receive funding opportunities through the Smith Family Clinic for Genomic Medicine’s Hero Fund. Please contact the laboratory for details. To reach the HudsonAlpha Clinical Services Lab, LLC., directly, call 256-327-9670 or email us at firstname.lastname@example.org.
The HudsonAlpha Clinical Service Lab will not begin processing samples until payment arrangements have been made. The responsible party must pay 100% of the test price prior to initiating testing. The test request form includes payment options (credit card, debit card, flex spending card, wire transfer or personal check). Please contact the HudsonAlpha Clinical Service Lab to arrange payment via wire transfer or check. The HudsonAlpha Clinical Service Lab can only accept credit cards from inside the United States at this time; international customers should contact the HudsonAlpha Clinical Service Lab to arrange a different payment option. Payment arrangements can include payment by check, credit card, or approved purchase order. Payments by credit card will be subject to a 3% processing fee, as assessed by our credit card processor.
Payment by check shall be made payable to The HudsonAlpha Clinical Services Lab, LLC. 601 Genome Way, Huntsville, AL 35806.
What are the secondary findings in the reports?
Secondary or incidental findings in whole genome sequencing and tertiary analysis In the process of analyzing a genome looking for a disease-causing variant, the laboratory may identify an incidental finding, which is a pathogenic variant that is not connected to the patient’s clinical presentation but may have implications for their health. For example, an analysis of a child with a seizure disorder may uncover a pathogenic variant in BRCA1, a gene associated with hereditary breast and ovarian cancer. Such a finding may be relevant to both the patient undergoing whole genome sequencing and other members of their family.
Our test form contains relevant information about the types of secondary or incidental findings that can be reported back to the ordering physician. Patients can choose to have no incidental findings reported, or select from several other options including untreatable childhood disorders (e.g. Tay-Sachs Disease), treatable adulthood disorders (e.g. hereditary colon cancer), untreatable adulthood disorders (e.g. Alzheimer Disease) and disease carrier status (e.g. phenylketonuria). Genetic counseling can be helpful as patients (and families) make these decisions.
There is no such thing as a perfect genetic test. Whole genome sequencing is powerful but cannot detect all types of genetic variation that may contribute to or cause disease. For example, trinucleotide repeat disease including fragile X syndrome, Huntington’s disease, a variety of ataxias and others are not well assessed by whole genome sequencing. A negative result in a genome sequencing test does not rule out the possibility of a genetic condition.
Who do I contact for any billing questions?
The HudsonAlpha Clinical Services Lab is customer-focused. Our team members have advanced degrees and are highly experienced in the design and completion of next-generation sequencing projects of all types. They bring extensive experience and knowledge that enable us to provide the best in support. Success begins with the design of the project, the efficient execution of the project, analysis of the data and supporting the customer to ensure that the data and reports generated will meet their needs. To achieve all of these goals we have teams for each project who work with the customer to ensure that we understand their needs and meet them to the customer’s satisfaction. After completion of the project, we continue to support your needs and are available to answer your questions and assist you in reviewing the information that we have generated. Please contact us for any billing questions at 256-327-0438.