Table 1.

Summary of NGS-NBS and Diagnostic Findings in the NC NEXUS Study

NC NEXUS Cohort	Total Number of Participants in Cohort	NGS-NBS Abnormal Positive Screen	NGS-NBS Normal Negative Screen	Diagnostic Positive	Diagnostic Inconclusive	Diagnostic Negative
Metabolic	17	15	2	15	2	0
Hearing loss	28	7∗	21	5	5	18
Healthy/well-child	61	1∗	60	0	0	0
Sum
Unanticipated findings	106	4	N/A	N/A	N/A	N/A

An abnormal NGS-NBS, or positive screen, was indicated by observing likely pathogenic and/or pathogenic variants in genes associated with pediatric conditions with high medical actionability. A normal NGS-NBS, or negative screen, was defined by the absence of likely pathogenic or pathogenic variants found in these genes. Diagnostic positive indicates the presence of likely pathogenic or pathogenic variants found in gene(s) on the metabolic or hearing loss diagnostic list that are consistent with the participant’s disorder. Diagnostic inconclusive indicates an inconclusive result (i.e., a single heterozygous variant found in a gene associated with an autosomal-recessive condition and/or variants of uncertain significance [VUS] in genes on the diagnostic list). A negative diagnostic result indicated that we did not detect any pathogenic or likely pathogenic variants or any VUS on the diagnostic gene lists. Numbers with asterisks include two participants in the hearing loss cohort with an abnormal NGS-NBS due to likely pathogenic variants in DSC2 or F11 plus one participant in the healthy/well-child cohort that was determined to have an abnormal NGS-NBS due to a pathogenic variant in LDLR associated with familial hypercholesterolemia. NGS-NBS, next-generation sequencing newborn screen.