Genetics Insider: September 2020

Literature review 
Did you catch what our colleagues are doing? 

Increasing uptake of BRCA testing for women with high-grade serous ovarian cancer

BRCA genetic variants are present in up to 15% of patients with high-grade serous carcinoma of the ovaries, fallopian tubes, or peritoneum. A new study from McGill University in Montreal, published in the International Journal of Gynecological Cancer, shows that BRCA1 and BRCA2 testing initiated at the time of diagnosis can increase testing uptake and decrease testing delays when compared with a traditional genetic testing model:

  • This retrospective study included 108 women diagnosed with high-grade serous ovarian, tubal, or peritoneal cancer who were referred to medical genetics for multi-gene testing that included BRCA1 and BRCA1. Also included were 44 women with the same diagnoses who were part of a subsequently launched program in which genetic testing was initiated at the time of diagnosis by their gynecologic oncologists.
  • Uptake of genetic testing improved from 50.9% to 86.2% once the new testing program began.
  • Introduction of the program decreased the median time from diagnosis to genetic testing by 114 days and the median time from diagnosis to disclosure of test results by 128 days. Both of these results were statistically significant. 
  • Early identification of BRCA variants in women with high-grade serous ovarian and related cancers may improve access to treatment with PARP inhibitors and facilitate more timely genetic test results for these women.


Practical guidance for managing patients with metastatic castration-resistant prostate cancer

A panel of 14 experienced urologists and medical oncologists have released new guidance on managing patients with metastatic castration-resistant prostate cancer. Published in a review article in The Prostate, the new guidance complements national guidelines and is intended for providers from all practice settings who evaluate and manage patients with advanced prostate cancer:

  • The guidance focuses on four areas: 1) biomarker monitoring and the role of genetic and molecular testing; 2) rationale, current strategies, and optimal sequencing of approved therapies; 3) management and monitoring of adverse events; and 4) imaging of advanced prostate cancer.
  • The panel largely agreed with National Comprehensive Cancer Network (NCCN) guidelines regarding the role of genetic and molecular testing. Panel members unanimously agreed that genetic testing should be performed at the time of diagnosis, that genetic consultation with a genetic counselor or other educated provider is necessary in this context, and that medical providers who see patients with advanced prostate cancer should continue to educate themselves about genetic testing. 
  • The guidance also suggests that more genetic counselors with expertise in oncology are needed to meet the need for genetic consultation in this field.


Need for consistent terminology in genetic testing for precision medicine in oncology

Precision medicine in oncology is only possible if the biomarkers and germline genetic variants in a cancer patient’s tumor or other biospecimen are known and understood. However, many patients don’t know how to communicate with their providers about genetic testing to uncover these characteristics, in part because of a lack of consistent terminology about the tests. The LUNGevity Foundation convened a working group to develop consistent, simple language that can be used by a variety of stakeholders including patient advocates, providers, and policy makers to talk about genetic testing for precision medicine. The recommendations of the working group have been published as a white paper:

  • The group identified 33 terms used in patient education and clinical care to discuss genetic testing for precision medicine. Many times, multiple terms were used to describe the same test. In other cases, one term was used to describe more than one type of test. For example, “genetic testing” sometimes referred to testing for somatic (i.e., acquired) variants and sometimes referred to testing for germline (i.e., inherited) variants, depending on the setting.
  • The working group recommends using the term “biomarker testing” to refer to testing for somatic variants or other biomarkers and the term “genetic testing for inherited cancer risk” to refer to testing for germline variants.
  • If widely accepted, this new terminology could help patients better understand the different types of testing and how their test results could inform decisions about their care. 

Genetic testing for cardiovascular diseases 

new scientific statement from the American Heart Association highlights how genetic testing can improve diagnosis and management of individuals with cardiovascular conditions ranging from inherited arrhythmias to cardiomyopathies, familial hypercholesterolemia, and inherited vascular disorders:

  • Genetic testing can help classify subtypes or support clinical diagnoses. 
  • For genetic arrhythmias such as long QT syndrome, a molecular diagnosis may affect recommended treatment and risk assessment.
  • In the cardiomyopathies (the largest group of conditions), pinpointing the specific type of variant may allow a patient to receive experimental treatments or may identify patients in need of an implantable cardioverter defibrillator. 
  • A genetically confirmed diagnosis of familial hypercholesterolemia can affect the choice of lipid-lowering therapies, including possibly more aggressive regimens. 
  • For inherited vascular disorders such as familial thoracic aortic aneurysm and dissection, a molecular diagnosis can affect the timing of recommended surgical intervention and the type and extent of vascular screening. 



Genetic testing changes clinical management of pediatric epilepsy

In a recent study published in Clinical EEG and Neuroscience, researchers looked for changes in clinical management of 91 pediatric epilepsy patients who underwent panel-based testing based on next-generation sequencing:

  • Pathogenic or likely pathogenic variants were found in 16 patients, and the genetic diagnosis changed the clinical management for 10 (63%) of them. Median age at testing was 5.3 years.
  • For seven (44%) of the molecularly diagnosed patients, drug regimens were changed. For five patients with SCN1A-related epilepsy, genetic test results led to reduction or elimination of sodium channel blockers—an important change, as these drugs can increase seizure frequency in SCN1A patients.
  • In eight (50%) of the patients with diagnostic findings, invasive or cumbersome diagnostic procedures such as magnetic resonance imaging under general anesthesia were avoided.
  • The findings suggest that early uptake of genetic testing for pediatric epilepsy patients could reduce unnecessary and potentially harmful diagnostic procedures and treatment


Causal genetic variants in stillbirth

There are limited data on monogenic disorders that may be responsible for stillbirth, and its cause remains largely unknown. A study in The New England Journal of Medicine evaluated the diagnostic utility of clinical exome sequencing in 246 stillbirth cases:

  • A molecular diagnosis was identified in 15 (6.1%) of 246 stillborn cases. Nine of these cases had variants in seven genes known to be involved with stillbirth, and six had variants in six strong candidate genes.
  • Among the stillbirth cases, a case-control analysis showed an enrichment of loss-of-function variants in genes that are intolerant to genetic variation and have not been associated with human disease in OMIM. 
  • This study did not include parental genotypes and could not identify compound heterozygotes or provide information on inheritance to interpret novel missense variants. However, based on prior literature, the authors propose that family trio sequencing in the analysis of stillbirths could double the diagnostic yield in known stillbirth genes.
  • When combining the data from this study with previous results in this cohort, 18% of stillbirths were found to have a known genetic cause.



Committee opinion on clinical management of mosaic results from preimplantation genetic testing for aneuploidy 

With advances in technology increasing the ability to detect and report mosaicism for aneuploidy in embryonic trophectoderm biopsies, there is much discussion on how to interpret these findings and whether embryos with a mosaic result should be stored and transferred. An opinion piece from the Practice Committee and Genetic Counseling Professional Group of the American Society for Reproductive Medicine (ASRM), published in Fertility and Sterility , reviews the literature and outlines various considerations regarding clinical management:

  • The diagnosis of mosaicism is inferred from the presence of an intermediate chromosome copy number. Therefore, an intermediate copy number on a  pre-implantation genetic testing for aneuploidy (PGT-A) result indicates that the biopsied embryo may be at risk of mosaicism, but this cannot be confirmed through clinical testing.
  • There are currently no evidence-based clinical guidelines in the United States to determine which embryos with mosaic results should be considered for transfer.
  • If the detection and reporting of mosaicism will be included in a clinic’s policy, comprehensive pre- and post-test counseling are recommended. Before transferring an embryo with a mosaic result, patients should be informed of the chances for failed implantation or miscarriage, options for prenatal screening and diagnostic testing, and potential management considerations if a pregnancy is found to be affected with the aneuploidy detected.
  • There are limited post-transfer outcome data and almost no long-term data on the health of pregnancies and children for embryos with mosaic results. Providers are encouraged to publish the phenotypic information and chromosomal data for resulting pregnancies.



Invitae news
Here’s what we’ve been up to

Panel updates

You asked for more content in your genetic tests. We heard you, and this month added additional genes and panels to our test catalog, including:

  • Five new and two updated metabolic, pediatric, and immunology panels. View the new and updated panels here or place an order in the Invitae test catalog.
  • Panels associated with Invitae’s no-charge, sponsored testing programs have also been updated. Please visit to select and view a program.
  • Please note: These panels are pending New York State approval.



Buccal swab sample collection now available

For pediatric patients who are unable to submit a blood or saliva sample, buccal swabs make it possible to collect a quality DNA sample. We’ll even ship kits straight to your patients’ homes so they can get the answers they need sooner. Whether you opt for saliva, blood or buccal collection, you’ll get the same prices, quality, and service you know and trust. Request a kit.


Non-invasive prenatal screening

The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine (SMFM) recently updated their Practice Bulletin (Number 226 replaces Number 163) on Screening for Fetal Chromosomal Abnormalities. ACOG and SMFM recommend that prenatal genetic screening (including non-invasive prenatal screening, NIPS) and diagnostic testing should be discussed and offered to all pregnant patients, regardless of maternal age or risk. 1
Given the guideline update, we’d like to remind you that we’ve brought non-invasive prenatal screening (NIPS) in-house, which allows us to make significant enhancements based on feedback from GCs like you. Now we’re able to offer:

  • ≥99% sensitivity and specificity for common trisomies (view the validation white paper)
  • More customization options, including the ability to order specific microdeletions and to order sex chromosome abnormalities without revealing fetal sex
  • Improved report format (see positive and negative sample reports)
  • An improved patient experience that includes videos revealing the baby’s predicted sex in the patient portal


Breast Cancer Awareness Month

October is Breast Cancer Awareness Month, making it a busy month for many cancer genetic counselors. This year, Invitae will work to drive awareness about genetic testing and the role that it plays in breast cancer, especially given the current public health crisis that has caused many patients to delay important cancer screenings, like mammograms. 
As always, Invitae views genetic counseling as an important part of the genetic testing process. We will continue to drive patients and their doctors to our Genetics Provider Network (GPN) so they can more easily find you before, during, or after the testing process. If you have not yet done so, please join the network so that patients visiting our website can find you when they search for a genetic counselor in their area.
This and every month, we keep GCs at the heart of everything we do at Invitae!


Invitae and ArcherDX

In June, we announced an exciting development: Invitae and ArcherDX will be joining forces to create a global leader in comprehensive cancer genetics and precision oncology, to bring germline and somatic testing, liquid biopsy and tissue genomic profiling onto a single platform. Read more here.


Webinars: Keeping you informed

We’re dedicated to keeping you up to date on the most important issues in genetics today, especially at a time when many of us are unable to attend in-person conferences. Check out these recent webinars:

  • Upcoming CEU webinar: On Thursday, October 8 at 9:00 am Pacific, Invitae’s Sarah Garcia, PhD, MS, CGC, will present “Variant Interpretation 101: Back to Basics.” This is a great opportunity for new GCs and anyone looking for a refresher. Register today!
  • All Invitae webinars are recorded and available on-demand after the live presentation. See them here.


Sponsored testing

Invitae’s sponsored testing programs provide no-charge genetic testing to patients who meet certain eligibility criteria. Saliva kits can be shipped directly to patients for sample collection. Learn more here and see below for program updates:

  • New: The PTC Pinpoint™ CP Spectrum genetic testing program is available for individuals in the US and Canada with symptoms suggestive of cerebral palsy in the absence of risk factors for an acquired brain injury. 
  • New: The BRCA Care genetic testing program is currently available in select international regions for patients diagnosed with HER2-negative locally advanced or metastatic breast cancer (HER2- LA/mBC).
  • Expanded: The Alnylam Act® Acute Hepatic Porphyrias program is now available in Brazil, offering testing for individuals 16 years or older who may carry a gene mutation known to be associated with acute hepatic porphyria (AHP).


Honoring the heart that genetic counselors bring to patient care

Mark your calendars to recognize your profession with the emotional stories of what excellent care feels like to patients. Presented by the National Society of Genetic Counselors (NSGC) and Invitae, the Heart of Genetic Counseling Award pays tribute to the distinguished genetic counselors who provide exceptional and irreplaceable care to families dealing with major health challenges.

The distinguished nominees and finalists will be unveiled and one will be honored with the Heart of Genetic Counseling Award. Lindsay Avner, the Founder of Bright Pink, a leading national breast and ovarian health non-profit, will share her story and mission as a featured guest speaker.

You don’t want to miss the virtual award ceremony on November 19 at 4:30 pm Central.


This is us.
At Invitae, we always ask, “What is your Why?”

Why are we inspired by Invitae’s mission? Why do we get up every day and put 110% into our work? Here’s a little insight into why we’re dedicated to increasing access to genetic information for everyone.

There are many reasons why I chose the field of genetics, and many reasons why I chose Invitae. The “why” that weighs most on my mind currently is my mother-in-law, who passed away last week. She was diagnosed with breast cancer 6 years ago, and had been in remission for the last 4 years. One year ago, she was diagnosed with stage 4 metastatic gallbladder cancer that took a year to diagnose, at which point it was inoperable and essentially untreatable. Gallbladder cancer is quite rare, although it is more prevalent among Latinas for unknown reasons. Unless we continue to test people and further lower barriers to medical testing, we may never understand why. Never stop asking why and never cut corners. We should (and, at Invitae, we do) treat every test as if it belonged to our family member anxiously awaiting an answer. This motivates me every day, even on days as sad as this one.

—B. Monica Bowen, PhD | Clinical Genomics Scientist