The Answer ALS return of results study: Answering the duty to disclose.

The Return of Answer ALS Results (RoAR) Study was designed to provide a mechanism for participants in Answer ALS, a large, prospectively designed natural history and biorepository study to receive select clinical genetic testing results and study participants' experience with the results disclosure. Participants consented to receive results of five ALS genes () and/or 59 medically actionable genes as designated by the American College of Medical Genetics. Patient-reported genetic testing outcomes were measured via a post-disclosure survey.

Amyotrophic Lateral Sclerosis Genetic Access Program: Paving the Way for Genetic Characterization of ALS in the Clinic.

Objective: To report the frequency of amyotrophic lateral sclerosis (ALS) genetic variants in a nationwide cohort of clinic-based patients with ALS with a family history of ALS (fALS), dementia (dALS), or both ALS and dementia (fALS/dALS).

Methods: A multicenter, prospective cohort of 573 patients with fALS, dALS, or fALS/dALS, underwent genetic testing in the ALS Genetic Access Program (ALS GAP), a clinical program for clinics of the Northeast ALS Consortium. Patients with dALS underwent hexanucleotide repeat expansion (HRE) testing; those with fALS or fALS/dALS underwent HRE testing, followed by sequencing of , , , , and .

Novel heterozygous truncating titin variants affecting the A-band are associated with cardiomyopathy and myopathy/muscular dystrophy.

Background: Variants in TTN are frequently identified in the genetic evaluation of skeletal myopathy or cardiomyopathy. However, due to the high frequency of TTN variants in the general population, incomplete penetrance, and limited understanding of the spectrum of disease, interpretation of TTN variants is often difficult for laboratories and clinicians. Currently, cardiomyopathy is associated with heterozygous A-band TTN variants, whereas skeletal myopathy is largely associated with homozygous or compound heterozygous TTN variants.

Incidence of pathogenic, likely pathogenic, and uncertain ALS variants in a clinic cohort.

Objective: To determine the incidence of amyotrophic lateral sclerosis (ALS) genetic variants in a clinic-based population.

Methods: A prospective cohort of patients with definite or probable ALS was offered genetic testing using a testing algorithm based on family history and age at onset.

Results: The incidence of pathogenic (P) or likely pathogenic (LP) variants was 56.