Expanding the phenotypic spectrum of NOTCH1 variants: clinical manifestations in families with congenital heart disease.

Pathogenic variants in NOTCH1 are associated with non-syndromic congenital heart disease (CHD) and Adams-Oliver syndrome (AOS). The clinical presentation of individuals with damaging NOTCH1 variants is characterized by variable expressivity and incomplete penetrance; however, data on systematic phenotypic characterization are limited. We report the genotype and phenotype of a cohort of 33 individuals (20 females, 13 males; median age 23.

Testing and Management of Iron Overload After Genetic Screening-Identified Hemochromatosis.

Importance: HFE gene-associated hereditary hemochromatosis type 1 (HH1) is underdiagnosed, resulting in missed opportunities for preventing morbidity and mortality.

Objective: To assess whether screening for p.Cys282Tyr homozygosity is associated with recognition and management of asymptomatic iron overload.

Using whole genome sequence findings to assess gene-disease causality in cardiomyopathy and arrhythmia patients.

The genetic etiologies of cardiomyopathies and arrhythmias have not been fully elucidated. Research findings from genome analyses in a cardiomyopathy and arrhythmia cohort were gathered. Gene-disease relationships from two databases were compared with patient phenotypes.

Evaluation of Malignant Hyperthermia Features in Patients with Pathogenic or Likely Pathogenic RYR1 Variants Disclosed through a Population Genomic Screening Program.

Background: Malignant hyperthermia (MH) susceptibility is a heritable musculoskeletal disorder that can present as a potentially fatal hypermetabolic response to triggering anesthesia agents. Genomic screening for variants in MH-associated genes RYR1 and CACNA1S provides an opportunity to prevent morbidity and mortality. There are limited outcomes data from disclosing variants in RYR1, the most common MH susceptibility gene, in unselected populations.

Optimizing communication strategies and designing a comprehensive program to facilitate cascade testing for familial hypercholesterolemia.

Background: This project aimed to optimize communication strategies to support family communication about familial hypercholesterolemia (FH) and improve cascade testing uptake among at-risk relatives. Individuals and families with FH provided feedback on multiple strategies including: a family letter, digital tools, and direct contact.

Methods: Feedback from participants was collected via dyadic interviews (n = 11) and surveys (n = 98) on communication strategies and their proposed implementation to improve cascade testing uptake.

Elective genomic testing: Practice resource of the National Society of Genetic Counselors.

Genetic counseling for patients who are pursuing genetic testing in the absence of a medical indication, referred to as elective genomic testing (EGT), is becoming more common. This type of testing has the potential to detect genetic conditions before there is a significant health impact permitting earlier management and/or treatment. Pre- and post-test counseling for EGT is similar to indication-based genetic testing.

Motivating cascade testing for familial hypercholesterolemia: applying the extended parallel process model for clinician communication.

Motivating at-risk relatives to undergo cascade testing for familial hypercholesterolemia (FH) is critical for diagnosis and lifesaving treatment. As credible sources of information, clinicians can assist in family communication about FH and motivate cascade testing uptake. However, there are no guidelines regarding how clinicians should effectively communicate with probands (the first person diagnosed in the family) and at-risk relatives.

Genetic counseling for patients with positive genomic screening results: Considerations for when the genetic test comes first.

Emerging genetic testing delivery models have enabled individuals to receive testing without a medical indication. This article will highlight key considerations for patient care in the setting of adult patients with positive results for monogenic disease identified through genomic screening. Suggestions for how to adapt genetic counseling to a genomic screening population will encompass topics such as phenotyping, risk assessments, and the use of existing guidelines and resources.

Clinical Findings and Diagnostic Yield of Arrhythmogenic Cardiomyopathy Through Genomic Screening of Pathogenic or Likely Pathogenic Desmosome Gene Variants.

Background: Genomic screening holds great promise for presymptomatic identification of hidden disease, and prevention of dramatic events, including sudden cardiac death associated with arrhythmogenic cardiomyopathy (ACM). Herein, we present findings from clinical follow-up of carriers of ACM-associated pathogenic/likely pathogenic desmosome variants ascertained through genomic screening.

Methods: Of 64 548 eligible participants in Geisinger MyCode Genomic Screening and Counseling program (2015-present), 92 individuals (0.

Adopted individuals' interest in elective genomic testing.

Purpose: Adoptees are a population that could benefit from genetic testing to fill gaps in family health history (FHH). Elective genomic testing (EGT) provides adoptees with clinical genetic testing options to learn about genetic health risks in the absence of FHH. We assessed adoptees' interests in, motivations for and perceived utility of EGT.

The impact of the number of tests presented and a provider recommendation on decisions about genetic testing for cancer risk.

Objective: To determine how the method of presenting testing options and a provider recommendation can influence a decision about genetic testing for inherited cancer predispositions.

Methods: An online hypothetical vignette study was completed by 454 healthy volunteers. Participants were randomized to receive one of two survey versions which differed by genetic testing choice presentation.

Clinical outcomes of a genomic screening program for actionable genetic conditions.

Purpose: Three genetic conditions-hereditary breast and ovarian cancer syndrome, Lynch syndrome, and familial hypercholesterolemia-have tier 1 evidence for interventions that reduce morbidity and mortality, prompting proposals to screen unselected populations for these conditions. We examined the impact of genomic screening on risk management and early detection in an unselected population.

Methods: Observational study of electronic health records (EHR) among individuals in whom a pathogenic/likely pathogenic variant in a tier 1 gene was discovered through Geisinger's MyCode project.

Positive impact of genetic counseling assistants on genetic counseling efficiency, patient volume, and cost in a cancer genetics clinic.

Purpose: Cancer genetics clinics have seen increasing demand, challenging genetic counselors (GCs) to increase efficiency and prompting some clinics to implement genetic counseling assistants (GCAs). To evaluate the impact of GCAs on Geisinger's cancer genetics clinic, we tracked GC time utilization, new patient volume, and clinic cost per patient before and after implementing a GCA program.

Methods: GCs used time-tracking software while completing preappointment activities.

Patient assessment of chatbots for the scalable delivery of genetic counseling.

A barrier to incorporating genomics more broadly is limited access to providers with genomics expertise. Chatbots are a technology-based simulated conversation used in scaling communications. Geisinger and Clear Genetics, Inc.

A Model for Genome-First Care: Returning Secondary Genomic Findings to Participants and Their Healthcare Providers in a Large Research Cohort.

There is growing interest in communicating clinically relevant DNA sequence findings to research participants who join projects with a primary research goal other than the clinical return of such results. Since Geisinger's MyCode Community Health Initiative (MyCode) was launched in 2007, more than 200,000 participants have been broadly consented for discovery research. In 2013 the MyCode consent was amended to include a secondary analysis of research genomic sequences that allows for delivery of clinical results.

Generation and Implementation of a Patient-Centered and Patient-Facing Genomic Test Report in the EHR.

Context: Communication of genetic laboratory results to patients and providers is impeded by the complexity of results and reports. This can lead to misinterpretation of results, causing inappropriate care. Patients often do not receive a copy of the report leading to possible miscommunication.

Patient-Centered Precision Health In A Learning Health Care System: Geisinger's Genomic Medicine Experience.

Health care delivery is increasingly influenced by the emerging concepts of precision health and the learning health care system. Although not synonymous with precision health, genomics is a key enabler of individualized care. Delivering patient-centered, genomics-informed care based on individual-level data in the current national landscape of health care delivery is a daunting challenge.

Early cancer diagnoses through BRCA1/2 screening of unselected adult biobank participants.

PurposeThe clinical utility of screening unselected individuals for pathogenic BRCA1/2 variants has not been established. Data on cancer risk management behaviors and diagnoses of BRCA1/2-associated cancers can help inform assessments of clinical utility.MethodsWhole-exome sequences of participants in the MyCode Community Health Initiative were reviewed for pathogenic/likely pathogenic BRCA1/2 variants.