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Since the first novel gene discovery for a Mendelian condition was made via exome sequencing, the rapid increase in the number of genes known to underlie Mendelian conditions coupled with the adoption of exome (and more recently, genome) sequencing by diagnostic testing labs has changed the landscape of genomic testing for rare diseases. Specifically, many individuals suspected to have a Mendelian condition are now routinely offered clinical ES. This commonly results in a precise genetic diagnosis but frequently overlooks the identification of novel candidate genes. Such candidates are also less likely to be identified in the absence of large-scale gene discovery research programs. Accordingly, clinical laboratories have both the opportunity, and some might argue a responsibility, to contribute to novel gene discovery, which should, in turn, increase the diagnostic yield for many conditions. However, clinical diagnostic laboratories must necessarily balance priorities for throughput, turnaround time, cost efficiency, clinician preferences, and regulatory constraints and often do not have the infrastructure or resources to effectively participate in either clinical translational or basic genome science research efforts. For these and other reasons, many laboratories have historically refrained from broadly sharing potentially pathogenic variants in novel genes via networks such as Matchmaker Exchange, much less reporting such results to ordering providers. Efforts to report such results are further complicated by a lack of guidelines for clinical reporting and interpretation of variants in novel candidate genes. Nevertheless, there are myriad benefits for many stakeholders, including patients/families, clinicians, and researchers, if clinical laboratories systematically and routinely identify, share, and report novel candidate genes. To facilitate this change in practice, we developed criteria for triaging, sharing, and reporting novel candidate genes that are most likely to be promptly validated as underlying a Mendelian condition and translated to use in clinical settings., Competing Interests: Conflict of Interest All authors of this manuscript are funded by the NIH. Erica Smith is a current employee of Ambry Genetics and a stockholder of Invitae genetics. Megan H. Hawley is an employee of Invitae and own stock in the company. Michael J. Bamshad is the chair of the Scientific Advisory Board of GeneDx and receives funding from the American Society of Human Genetics as the Editor-in-Chief of HGG Advances. Jessica X. Chong receives funding from the American Society of Human Genetics as the Deputy Editor of HGG Advances. Heidi L. Rehm has received rare-disease research funding from Microsoft and Illumina and compensation as a past member of the scientific advisory board of Genome Medical., (Copyright © 2024 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

In the published version of this paper, some of the columns in the last three rows of Table 3 were mistakenly transposed. The corrected table appears below. In col. 6 of the row for DNMT3A, "S3" was published in the original article. However, in the revised table for the corrigendum, it has been corrected to "S1". In col. 6 of the row for SON, "S3" was published in the original article. However, in the revised table for the corrigendum, it has been corrected to "S2".

Purpose: Diagnostic exome sequencing (DES) is now a commonly ordered test for individuals with undiagnosed genetic disorders. In addition to providing a diagnosis for characterized diseases, exome sequencing has the capacity to uncover novel candidate genes for disease., Methods: Family-based DES included analysis of both characterized and novel genetic etiologies. To evaluate candidate genes for disease in the clinical setting, we developed a systematic, rule-based classification schema., Results: Testing identified a candidate gene among 7.7% (72/934) of patients referred for DES; 37 (4.0%) and 35 (3.7%) of the genes received evidence scores of "candidate" and "suspected candidate," respectively. A total of 71 independent candidate genes were reported among the 72 patients, and 38% (27/71) were subsequently corroborated in the peer-reviewed literature. This rate of corroboration increased to 51.9% (27/52) among patients whose gene was reported at least 12 months previously., Conclusions: Herein, we provide transparent, comprehensive, and standardized scoring criteria for the clinical reporting of candidate genes. These results demonstrate that DES is an integral tool for genetic diagnosis, especially for elucidating the molecular basis for both characterized and novel candidate genetic etiologies. Gene discoveries also advance the understanding of normal human biology and more common diseases.Genet Med 19 2, 224-235.

Objective: To determine the reliability and validity of a 10-item questionnaire, the Food Label Literacy for Applied Nutrition Knowledge questionnaire., Methods: Participants were elementary school children exposed to a 90-minute school-based nutrition program. Reliability was assessed via Cronbach α and intraclass correlation coefficient (ICC). Validity was assessed comparing the questionnaire's food choices using an objective metric of nutrition quality, the Overall Nutritional Quality Index (ONQI), via t test. Statistical significance was set at .05., Results: Four hundred ninety-nine children participated, 51% were female, and the average age was 8.6 (± 0.9) years. Cronbach α = .77 and ICC = 0.68 (between administrations) were observed. ONQI scores of correct responses were significantly higher when compared to the ONQI scores of incorrect responses (27.4 ± 9.4 vs 16.2 ± 9.4; P = .01)., Conclusions and Implications: The Food Label Literacy for Applied Nutrition Knowledge questionnaire was found to be both reliable and a valid measure of food label literacy in children taught the Nutrition Detectives program., (Copyright © 2012 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.)