Provider FAQs: Specimen requirements, shipping and sample failures

Specimen requirements

What are Invitae's specimen requirements?
Does Invitae provide specimen collection kits?
What paperwork is required with each specimen?
Does Invitae accept DNA extracted in other laboratories?
Can you arrange a blood draw for my patient?
Do you accept post-mortem specimens?
Do you accept fetal specimens?
Are there any special instructions for saliva specimens?
Invitae's saliva sample collection kit provides the materials and instructions for collecting and stabilizing saliva specimens. Please do not use buccal swabs or any other collection kit.
Before collecting a saliva sample using Invitae's kit, do not remove the plastic film from the funnel lid. The following tips can optimize saliva collection:
Before providing the sample, the patient should not drink (even water) for 30 minutes
Collecting saliva too soon after drinking anything, including water, dilutes saliva and reduces the amount of DNA.
Before providing the sample, the patient should not eat, smoke, or chew gum for 30 minutes
In addition to diluting the sample, eating could introduce non-human DNA to the sample.
Bubbles do not count
Make sure that the liquid saliva reaches the “Fill to” line; any bubbles should be above the line. This will ensure that enough saliva is collected.
Ongoing medical treatment
If the patient is undergoing medical treatment that reduces their white blood cell count (such as chemotherapy), it’s best to wait until the white blood cell count has returned to normal before providing a saliva sample.
It’s easier to collect large amounts of saliva in the mouth before spitting (rather than spitting small amounts more often).
It takes most people 2 to 5 minutes to provide a saliva sample. If your patient is still having trouble, the following suggestions can help increase saliva production:
Closing the mouth and wiggling the tongue
Gently rubbing the outside of the cheeks, just behind the back teeth
Making chewing motions with the mouth
Smelling or imagining smelling sour foods such as lemons
Thinking about one's own favorite food
If the suggestions above don’t work, try placing a few granules of sugar (just enough to taste it) or one drop of lemon juice on the tongue. This small amount of food won’t affect the results and could help stimulate saliva.
Once the patient is ready to provide a saliva sample, follow these steps:
Ask the patient to spit into funnel until the amount of liquid saliva (not bubbles) reaches the fill line.
Hold the tube upright with one hand. Close the funnel lid with the other hand by firmly pushing the lid until you hear a loud click. The liquid in the lid will be released into the tube and mixed with the saliva. Make sure that the lid is closed tightly. We request that a full 2 mL of saliva be donated prior to capping the kits to be valid for our genomic analysis. Should you not have completed the 2-mL donation before capping the tube, please request another collection kit.
Hold the tube upright. Unscrew the funnel from the tube.
Use the small cap to close the tube tightly.
Shake the capped tube for 5 seconds. Discard or recycle the funnel.
Multilingual user instructions and instructional videos are available online for both the US kits and international kits.
After completing the saliva donation, there are no special storage requirements for shipping the tube to Invitae. The saliva kit is stable at room temperature. For more information, please contact Client Services.
Are there any special instructions for buccal swab specimens?
All required materials for collection and detailed instructions are included in every kit.
Collection precautions
Ensure the sponge tip does NOT come into contact with any surface prior to collection.
The patient should not eat, drink (including water), smoke or chew gum or put anything in their mouth 30 minutes prior to collecting a sample. Babies should not breastfeed 30 minutes prior to collection.
Choking hazard. Caution should be used when inserting sponge into the mouth.
Do NOT ingest the swab or tube liquid. Wash with water if the tube liquid comes in contact with eyes or skin. Click here to view the device safety data sheet.
Collection instructions
Open package and remove collector without touching sponge tip. Place sponge as far back in the mouth as comfortable and rub along the lower gums in a back and forth motion. Gently rub the gums 10 times. If possible, avoid rubbing the teeth.
Gently repeat rubbing motion on the opposite side of the mouth along the lower gums an additional 10 times.
Hold the tube upright to prevent the liquid inside the tube from spilling. Unscrew the blue cap from the collection tube without touching the sponge.
Turn the cap upside down, insert the sponge into the tube and close cap tightly.
Invert the capped tube and shake vigorously 10 times.
Click here to view detailed instructions with step-by-step illustrations.
Click here to view an instructional video.
Additional notes
Kit intended use: This product is designed for the collection and stabilization of DNA from human oral samples.
Kit contents: 2 ORAcollectDx OCD-100 collection devices
Multilingual user instructions and instructional videos are available online for both the US kits and international kits..
For more information, please contact Client Services.
Are there any special instructions for assisted saliva specimens?
Invitae's saliva sample collection kit provides the materials and instructions for collecting and stabilizing saliva specimens.
Before collecting a saliva sample the patient should not eat, drink, smoke, or chew gum for 30 minutes. Do not offer mother’s milk or formula to infants in the 30 minutes prior to sample collection. In addition, do not remove the plastic film from the funnel lid.
Sample collection from infants and young children can take time. It can be helpful to provide entertainment or distraction for the patient to improve their tolerance. While collection is not at all painful, it does involve the patient holding their mouth open for periods of time while a person collects their saliva.
Place sponge in mouth, running along the cheek and the gums. Saliva often accumulates under the tongue, so swirling the sponge in this area can help with sample collection.
Insert saturated sponge in V-notch of funnel and wring the saliva out, allowing the saliva to release into the tube.
Repeat collection steps until saliva reaches the fill line.
Close the lid tightly until you hear a loud click. Unscrew the funnel from the tube, place the small cap on tightly, and shake for a few seconds.
Multilingual user instructions and instructional videos are available online for both the US kits and international kits.
After completing the saliva donation, there are no special storage requirements for shipping the tube to Invitae. The saliva kit is stable at room temperature. For more information, please contact Client Services.
What is the minimum age requirement for a child to use the saliva kits?
How long does Invitae retain a specimen?
My patient has a hematologic malignancy/condition. What are the limitations with testing?
Patients with certain active hematological conditions may have circulating leukocytes containing abnormal somatic variants. Leukocytes are found in blood, saliva and buccal specimens. The presence of these somatic variants can affect testing in the following ways:
A complete test failure
A partial test failure (i.e., deletion/duplication analysis failure)
Changes in the tumor cell line can conceal inherited variants and a false negative may occur
Changes in the tumor cell line can appear to be inherited and a false positive may occur
Therefore, the testing of blood, saliva, or buccal specimens is not recommended for patients with certain active hematological conditions. Instead, genomic DNA (gDNA) extracted from cultured skin fibroblasts is the preferred specimen type to evaluate for germline variants.
In order to determine which conditions to which the above limitations/recommendations are applicable, please refer to our specimen requirements page and specimen selection guide.
Finally, it is important to note that we are unable to accept blood, saliva, assisted saliva, and buccal swab samples from patients who have had an allogeneic (non-self) bone marrow or stem cell transplant, a liver transplant or have had a blood transfusion containing leukocytes less than two weeks prior to specimen collection.
My patient just had an MRI/CT with contrast, should we wait to draw their blood?
How many days after a blood transfusion can you draw a patient’s blood?

Shipping

How do I send a specimen to Invitae?
Does Invitae pay for shipping?
Does Invitae accept weekend or holiday deliveries?
How quickly after the blood draw does a specimen need to be shipped to Invitae?

Sample failures

What are the different types of test failures for diagnostic and genetic risk tests?
Test failures can and will occur in a small percentage of specimens. Failing specimens ensures that all reportable results perform to the quoted reported sensitivity and specificity. There can be several different types of test failures and while we may not be able to determine the specific reasons, we attempt to categorize them for guidance on potential next steps with the clinician’s correlation.
For our diagnostic and genetic risk tests, a specimen failure will be categorized as one of the following five types: Lab Processing Failure, Specimen Did Not Meet Quality Metrics, Specimen Did Not Meet Quality Metrics (Saliva Specific), Contamination Detected, and Mosaic Aneuploidy Detected. In addition, our diagnostic and genetic risk tests can also have one of the two following failures: Deletion/Duplication Analysis Failure and Deletion/Duplication Analysis Not Available on Saliva. Lastly, RNA analysis and skin punch biopsy specimens may have their own failure type.

Laboratory Processing Failure
Laboratory processing refers to the steps that a specimen undergoes to prepare and extract the DNA for analysis. After a specimen arrives at Invitae and is accessioned, its DNA is extracted and samples are placed on plates to enter our NGS sequencers. A lab processing failure occurs when there is an issue with the accessioning, extracting, or plating process. It can also occur if there is an issue with one of the sequencers when we attempt to obtain the data for analysis. Often lab processing failures are unique and do not occur again, however Invitae has a culture of continuous improvement that includes monitoring trends in performance, identifying opportunities for improvement, implementing corrective actions, and monitoring the effectiveness of those actions.
In general, laboratory processing failures are not related to specimen collection or conditions. They’re also not expected to be related to a patient’s underlying medical condition, such as hematologic malignancy, low white blood cell counts, or severe or metastatic disease.
If you receive a laboratory processing failure letter, please collect another specimen from your patient if possible. If you need assistance with ordering a collection kit or mobile phlebotomy services, please email clientservices@invitae.com. Specimen requirements and collection policies can be found on the specimen requirements page. Please ensure the collection tube is labeled with the patient’s full name, date of birth, and the RQ number so we can link the new specimen to the original order.
We understand that in some cases a new specimen is not an option. If this is the case, please email clientservices@invitae.com to cancel the order. Please note that there will be no bill for the cancelled order and a refund will be processed if the payment has already been submitted.

Specimen Did Not Meet Quality Metrics Failure
On occasion, a specimen will not yield the sufficient quality and/or quantity of DNA that is required for testing. This can occur if there was an overall low volume submitted, low white blood cells, or if there was clotted blood or degraded DNA due to the age of the specimen or conditions in which the specimen was obtained or transported. This type of failure may occur more frequently in individuals with certain health conditions such as severe and/or metastatic cancer, underlying hematological malignancy, or other conditions that result in low white blood cell counts. Recent chemotherapy or other treatments may also affect the quality and quantity of DNA in some patients, although the vast majority of individuals receiving chemotherapy treatment will be able to provide a specimen with sufficient quantity and quality of DNA for testing.
If this is the first specimen failure due to not meeting quality metrics, we will accept a new specimen at no additional charge to reattempt testing. To increase the chance for a successful retest, a blood specimen is recommended if possible (rather than, for example, a saliva specimen).
If, however, this is the second time this patient’s specimen failed, clinical correlation is recommended to assess for possible explanations such as the health conditions or treatments described above. A review of the clinical history may also help assess the appropriateness of submitting a third specimen or if an alternate specimen type should be considered. If desired, you can contact one of our clinical team members to discuss appropriate next steps by emailing clinconsult@invitae.com or by calling 800-436-3037.
For some patients undergoing chemotherapy, the treatment and/or metastatic disease/other health conditions will interact in a way that affects the success of the specimen. This effect can cause either a full test failure or a failure of the deletion/duplication analysis. When a specimen fails and chemotherapy/low white blood cells are a potential confounding factor, we recommend considering submitting a new specimen after the patient’s white blood cell counts have recovered and/or are more stable in their disease or health. Submitting additional tubes of blood beyond the requested amount will not be helpful in these cases.

Contamination Detected Failure
A failure for contamination means we detected DNA contamination from food material or other DNA sources that prevents us from proceeding with testing. The most common causes of contamination are eating or drinking prior to a saliva or buccal collection, improper blood collection, past allogeneic bone marrow or stem cell transplant, and blood transfusion less than two weeks before specimen collection.
If this is the first contamination-related specimen failure, we will accept a new specimen at no additional charge to reattempt testing. To increase the chance for a successful retest, a blood specimen is recommended if possible.
If, however, this is the second time this patient’s specimen failed due to contamination, clinical correlation is recommended to assess for the possibility of a biological explanation such as bone marrow or stem cell transplant, whether the patient was a product of a multiple gestation pregnancy, genetic chimerism, or other issues. A review of the clinical history can also help assess the appropriateness of submitting a third blood/saliva/buccal specimen or if an alternate specimen type should be considered. If desired, you can contact one of our clinical team members to discuss appropriate next steps by emailing clinconsult@invitae.com or by calling 800-436-3037.

Deletion Duplication Analysis Failure
Test failure of the deletion/duplication, also known as copy number variation (CNV), analysis occurs in a very small percentage of cases. The specific cause for CNV test failures is speculative and it is likely due to a variety of specific scenarios that have accumulated to affect the DNA quality/quantity in a manner that caused the failure. CNV failures are more common in individuals with severe and/or metastatic disease, underlying hematological malignancy, low white blood counts, or who have treatments such as chemotherapy or current health conditions that cause decreased white blood cell counts and/or DNA damage. In addition, the age of the specimen, certain tube types (e.g., gray top), and suboptimal sample conditions (e.g., frozen specimens, postmortem specimens) may contribute to test failures.
If the failure occurred with a blood or saliva specimen, we recommend submitting a new, preferably blood, specimen if possible.
While our tests utilize NGS technology for both the sequencing and deletion/duplication (CNV) analysis, the quality metrics, controls, and calling methods differ between the two components of the test. Therefore, any given specimen can have sufficient quality/data for the sequencing analysis but not the deletion/duplication analysis.
When a specimen passes the sequencing quality control metrics but fails the copy number variant (deletion/duplication) quality control metrics, the ordering provider can request to proceed in one of the three ways:
Proceed with the sequencing only report and current billing process, with the option to send in a new specimen at a later time at no additional charge for the deletion/duplication analysis.
Do not proceed with the sequencing only analysis, and instead send in a new specimen for another attempt at deletion/duplication analysis (and sequencing).
Request that the order be cancelled because a new specimen is not an option and the sequencing analysis alone is insufficient. The order will not be billed and a refund will be processed if the payment has been submitted.
If you would like to proceed with a new specimen for either option 1 or 2, Client Services can assist with sending a collection kit or arranging a mobile phlebotomy appointment (where available). Please ensure the collection tube is labelled with the patient’s full name, date of birth, and the RQ number so we can link the new specimen to the original order. To increase the chance for a successful retest, a blood specimen is recommended if possible.
If this is the second time this patient’s blood specimen failed, submitting a third blood specimen may not be recommended. If desired, you can contact one of our clinical team members to discuss appropriate next steps by emailing clinconsult@invitae.com or by calling 800-436-3037.
Note on gDNA samples: On all specimens, we attempt both sequencing and deletion/duplication analysis as available for your test selection, however the success rate of the deletion/duplication analysis can vary based on DNA quality. Testing gDNA that has been extracted at an external lab can lead to variability in DNA quality and therefore, deletion/duplication analysis on submitted gDNA is not guaranteed. Since gDNA deletion/duplication analysis is not guaranteed, we will automatically proceed with the sequencing only portion of the test and report. Since the failure letters that you may be familiar with on other tests are designed to notify of next step options, these are not released for gDNA deletion/duplication failures since a sequencing report will be provided automatically. The final sequencing report will have the deletion/duplication analysis failure noted in the Clinical Comments and Test Performed sections instead of a separate failure letter.
Frequency in panel testing: At Invitae, intragenic deletions and duplications (del/dups), or copy number variants (CNVs), are detected in approximately 10% of individuals with a clinically significant result (i.e., Pathogenic or Likely Pathogenic variants). However, it is important to note that the percentage of positive individuals with del/dup findings vary by clinical area, ranging from 5% in cardiology, 7% in hereditary cancer, 8% in metabolic disorders/newborn screening, 9% in immunology, 8% in pediatric genetics, 15% in epilepsy, and 39% in neurology. Neurology’s high percentage of deletion/duplication findings are related to CNVs in the PMP22, SMN1, and DMD genes in particular.
Deletions/duplications (CNVs) included in a sequencing only report: At Invitae, anything less than a full exon deletion/duplication can be detected with a sequencing only report. For example, if it is a familial variant case where the family member’s report states "Partial Deletion/Duplication (Exon 4)" or “c.1234del”, these variants would be detectable with a sequencing only report. If the familial variant is a full exon or larger, that would need CNV analysis to detect. For example, "Deletion (Exons 4-5)”, "Gain (Exon 5)", or Deletion (Entire coding sequence) would all require CNV analysis to detect.

Deletion Duplication Analysis Failure Due to Saliva
A small percentage of saliva specimens may contain artifact copy number variants (deletions/duplications) that reduce the ability to accurately detect/rule out germline copy number variants. These artifacts are typically found in saliva and not blood, so submitting a blood specimen to reattempt the analysis is recommended. If a saliva or buccal specimen is submitted instead, the same type of failure would be expected.

Specimen Did Not Meet Quality Metrics Failure (Saliva Specific)
A small percentage of saliva specimens may contain artifact variants that reduce the ability to accurately detect/rule out germline variants. These artifacts are typically found in saliva and not blood, so submitting a blood specimen to reattempt the analysis is recommended. If a saliva or buccal specimen is submitted instead, the same type of failure would be expected.

Mosaic Aneuploidy Detected Failure
Mosaic aneuploidy failures are due to the detection of what appears to be an abnormal amount of chromosomal material. The specific reason for this failure cannot be obtained from the data, but can be indicative of the the presence of constitutional mosaic aneuploidy (conditions such as mosaic trisomy or monosomy) or acquired somatic mosaic aneuploidy (which can be due to age-related changes, active hematological conditions, etc.) in the patient. We recommend a discussion with one of our clinical team members to review the patient’s history to determine if a new specimen is recommended. You can contact one of our clinical team members to discuss appropriate next steps by emailing clinconsult@invitae.com or by calling 800-436-3037.

RNA Analysis Failure
A small percentage of specimens will be unable to produce data that meets internal quality standards for the RNA analysis component of the test. When this occurs, the DNA analysis report will be released without delay and the RNA analysis failure will be noted in the “Clinical Comment” on the first page and the RNA analysis table will not be included in the report.
A specific reason for an individual RNA failure cannot regularly be determined from the data. However, some factors may increase the chances of a RNA failure. These include but are not limited to: an insufficient volume of whole blood was provided, extracted RNA amount and/or quality was insufficient for downstream tests, the blood specimen(s) clotted and/or RNA was degraded due to transportation delays or processing conditions. In addition, failures may occur more frequently in individuals with certain health conditions, low white blood cell counts, hematologic neoplasia, recent chemotherapy, or other treatments that may affect the quantity/quality of RNA. We can accept a new specimen at no additional charge to reattempt the analysis if desired.