Genetics Insider: March 2020

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Literature review
Did you catch what our colleagues are doing?

Update on genetic causes of long QT syndrome

In response to recent changes in our understanding of genetic variation, an international group of researchers has re-evaluated gene-disease associations in long QT syndrome (LQTS). The results are reported in the journal Circulation.

  • Three groups of researchers separately applied the ClinGen gene curation framework to review evidence for 17 genes previously reported to cause LQTS.

  • Only three genes had definitive evidence for causality in typical LQTS, and four had strong or definitive evidence for causality in LQTS with atypical features. 

  • Nine genes had limited or disputed evidence for causality. 

  • Genes with limited or disputed evidence should not be routinely tested in families with LQTS, while genes with evidence for causality in LQTS with atypical features should be tested when warranted by clinical observation.

Clinical utility of genetic testing for pediatric inherited eye disorders

An article in Genetics in Medicine supports genetic testing as an important diagnostic tool for inherited pediatric eye disorders.

  • Panel-based genetic testing was conducted for 201 children ages 0–5 with bilateral cataracts, bilateral anterior segment dysgenesis, bilateral ectopia lentis, albinism, or inherited retinal disorders.

  • Sixty-four percent of the children received a probable molecular diagnosis as a result of testing. 

  • Test results informed or altered clinical management for 33% of the children (e.g., by preventing unnecessary tests or improving prognostic certainty).

Prenatal exome sequencing for fetuses with structural abnormalities

Results of a prospective cohort study, published in The Lancet, confirm that whole-exome sequencing can facilitate the diagnosis of genetic disorders in fetuses with structural abnormalities detected by ultrasound.

  • After aneuploidy and large copy number variants were ruled out, whole-exome sequencing was performed on samples from 601 fetuses with structural abnormalities to evaluate genetic variants in 184 genes associated with developmental disorders.

  • Pathogenic/likely pathogenic variants were identified in 52 (8.5%) of the fetuses, and variants of uncertain significance that had potential clinical usefulness were identified in another 24 (3.9%). 

  • The addition of whole-exome sequencing to routine microarrays increases the number of genetic diagnoses in fetuses with structural abnormalities, allowing better predictions of fetal prognosis and future pregnancy risks.

Cost-effectiveness of multi-gene testing for breast cancer

Multi-gene testing for all patients with breast cancer is more cost-effective than testing based on current guidelines, according to a study published in JAMA Oncology.

  • The lifetime costs and effects of multi-gene testing in the United Kingdom and United States were modeled from payer and societal perspectives, taking into account testing, counseling, prevention, treatment, and productivity loss for patients and their relatives.

  • The model assumed that one group of patients would all undergo BRCA1/BRCA2/PALB2 testing and another portion would undergo BRCA1/BRCA2 testing only if they had a family history or met clinical criteria (i.e., the current guidelines).

  • Results showed that testing all patients with breast cancer is not only extremely cost-effective but, after only one year of testing, could prevent more than 11,000 cases of breast and ovarian cancer and more than 3,000 deaths in the UK and US.

  • These findings support changing current guidelines and policies to encourage broader genetic testing for all patients with breast cancer.

Educating women with fragile X premutations

A booklet called Women’s Health and Fragile X Premutation was created to help women better understand the health implications of their premutations. A new study published in the Journal of Genetic Counseling evaluated the impact of the booklet on women’s knowledge.

  • A pre-test survey among 142 women with fragile X premutations showed a lack of knowledge about the risk of fragile X-associated primary ovarian insufficiency and of factors associated with triplet repeat expansion.

  • Among 64 women who received the booklet and completed a post-test survey, 83% said the booklet was helpful.

  • The surveyed women’s knowledge of the health risks of fragile X premutations increased significantly after reviewing the booklet (from a median score of 24 out of 37 on the pre-test to a median score of 28 out of 37 on the post-test), suggesting that the use of targeted educational materials may be helpful in narrowing identified knowledge gaps.

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

Prevalence of germline risk variants in bladder cancer

An article in Genetics in Medicine highlights Invitae’s collaboration with the Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and the Broad Institute to retrospectively evaluate the prevalence of germline risk variants in patients with bladder cancer.

  • Next-generation sequencing was used to determine the frequency of pathogenic/likely pathogenic variants in 1,038 patients with high-risk bladder cancer.

  • Twenty-four percent of patients had pathogenic/likely pathogenic variants, 18.6% had variants for which the National Comprehensive Cancer Network recommends enhanced screening and family genetic testing, and 11% had variants that could inform therapeutic decisions. 

  • These results support both the clinical utility of germline testing in selected bladder cancer patients and the need to develop testing guidelines.

Functional Modeling Platform: Actionable information, sooner

Invitae’s Functional Modeling Platform (FMP) provides clarity for patients with variants of uncertain significance (VUS). Specifically, it informs missense variants, which are found in more than 1 in 4 patients tested at Invitae. When applied to previously reported variants, Invitae’s FMP has provided a more definitive variant classification for more than 5,000 patients over the past 6 months. FMP is now incorporated across ~700 genes for all patients who undergo genetic testing at Invitae. Want to learn more? Download our white paper.

Invitae’s approach to analyzing AGG interruptions for precise fragile X carrier risk assessment

Did you know that Invitae’s next-generation sequencing assay and bioinformatics solution accurately determines the location and number of AGG interruptions within the CGG repeat tract of FMR1 to provide a precise assessment of carrier risk for fragile X syndrome? Read our white paper to learn more.

Gene-specific results guides

Sometimes the hardest part is helping patients and their referring providers understand what the results mean and how to act on them. To help make your job easier, we’ve developed a series of nearly 150 gene-specific results guides that contain detailed descriptions of genes, related conditions and symptoms, as well as medical management guidelines and actionable next steps.

Making an impact with chromosomal microarrays

Bringing genetic information to all patients who can benefit from it is an important part of Invitae’s mission and we’re proud to say that we’ve now analyzed results from more than 65,000 chromosomal microarrays. Learn more about what sets apart Invitae’s chromosomal microarray analysis for pediatric disorders.

Invitae webinars: Keeping you informed

As our knowledge of genetics rapidly evolves, Invitae’s webinar series offers a way for you to stay up to date with the most important issues. All webinars are recorded and available on-demand after the live presentation.

Diagnostic yield and precision medicine implications from genetic testing in epilepsy

Learn about a study of >9,700 individuals tested with the Invitae Epilepsy Panel, including the benefits of early detection and potential precision medicine implications. Register to view >

Integrating functional modeling to enhance clinical variant interpretation

Invitae’s functional modeling removes the limitations of existing approaches to variant interpretation to provide clarity to patients with variants of uncertain significance. Register to view >

Invitae Boosted Exome: Providing affordable, transparent, clinically relevant results

Take an in-depth look at the Invitae Boosted Exome and learn how our unique method sets us apart from other exome tests on the market. Register to view >

NEW: We are excited to announce that in 2020 we will be offering CEUs to genetic counselors who participate in our webinars. 

Take a look at our upcoming webinars and view previous ones here: Please note that CEUs will be granted for select webinars throughout the year and only to live participants.


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.

“My ‘Why’ is the unknown surrounding the breast cancer that runs in my family. My cousin recently found out she has breast cancer. She is 37 years old and has five daughters. I am confident that in time we will know more about this disease and that this knowledge will empower the future generations of my family.”

—Sasha Christensen, international sales & business development


View the previous editions of Genetics Insider:

• March 2019

• January 2019

• November 2018

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