ArticleGenetics in medicine : official journal of the American College of Medical Genetics2017
Variants of uncertain significance in newborn screening disorders: implications for large-scale genomic sequencing.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Principles of Genomic Newborn Screening Programs: A Systematic Review.JAMA network open · 2021Pooled it
- digitalMLPA EZtec-MS: A new highly multiplexed DNA probe-based technique for neonatal screening.European journal of human genetics : EJHG · 2026Article
- Classical Homocystinuria Incidentally Diagnosed Following a Normal Newborn Screening Result.International journal of neonatal screening · 2026Article
- Article
- Refining CFTR-Related Metabolic Syndrome (CRMS)/Cystic Fibrosis Screen Positive, Inconclusive Diagnosis (CFSPID) Diagnosis: Impact of CFTR2 Variant Classifications.International journal of neonatal screening · 2025Review
- Rapid whole genome sequencing in newborn screening for metabolic diseases.Frontiers in pediatrics · 2025Review
- Tandem mass spectrometry in screening for inborn errors of metabolism: comprehensive bibliometric analysis.Frontiers in pediatrics · 2025Review
- Future of Dutch NGS-Based Newborn Screening: Exploring the Technical Possibilities and Assessment of a Variant Classification Strategy.International journal of neonatal screening · 2024Article
- Specifications of the ACMG/AMP guidelines for ACADVL variant interpretation.Molecular genetics and metabolism · 2023Article
- Parental Preferences for Expanded Newborn Screening: What Are the Limits?Children (Basel, Switzerland) · 2023Article
- Characterization of exonic variants of uncertain significance in very long-chain acyl-CoA dehydrogenase identified through newborn screening.Journal of inherited metabolic disease · 2022Article
- Utility of Whole Genome Sequencing for Population Screening of Deafness-Related Genetic Variants and Cytomegalovirus Infection in Newborns.Frontiers in genetics · 2022Article
- Use of Molecular Genetic Analyses in Danish Routine Newborn Screening.International journal of neonatal screening · 2021Article
- The low excretor phenotype of glutaric acidemia type I is a source of false negative newborn screening results and challenging diagnoses.JIMD reports · 2021Article
- Editorial: Newborn Screening for Inborn Errors of Metabolism: Is It Time for a Globalized Perspective Based on Genetic Screening?Frontiers in genetics · 2021Article
- Development of Strategies to Decrease False Positive Results in Newborn Screening.International journal of neonatal screening · 2020Review
- Two novel mutations in DNAJC12 identified by whole-exome sequencing in a patient with mild hyperphenylalaninemia.Molecular genetics & genomic medicine · 2020Article
- The Combined Impact of CLIR Post-Analytical Tools and Second Tier Testing on the Performance of Newborn Screening for Disorders of Propionate, Methionine, and Cobalamin Metabolism.International journal of neonatal screening · 2020Article
- A pediatric perspective on genomics and prevention in the twenty-first century.Pediatric research · 2020Review
- Value of genetic analysis for confirming inborn errors of metabolism detected through the Spanish neonatal screening program.European journal of human genetics : EJHG · 2019Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeAs exome and genome sequencing using high-throughput sequencing technologies move rapidly into the diagnostic process, laboratories and clinicians need to develop a strategy for dealing with uncertain findings. A commitment must be made to minimize these findings, and all parties may need to make adjustments to their processes. The information required to reclassify these variants is often available but not communicated to all relevant parties.
methodsTo illustrate these issues, we focused on three well-characterized monogenic, metabolic disorders included in newborn screens: classic galactosemia, caused by GALT variants; phenylketonuria, caused by PAH variants; and medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, caused by ACADM variants. In 10 years of clinical molecular testing, we have observed 134 unique GALT variants, 46 of which were variants of uncertain significance (VUS). In PAH, we observed 132 variants, including 17 VUS, and for ACADM, we observed 64 unique variants, of which 33 were uncertain.
conclusionAfter this review, 17 VUS (37%; 7 in ACADM, 9 in GALT, and 1 in PAH) were reclassified from uncertain (6 to benign or likely benign and 11 to pathogenic or likely pathogenic). We identified common types of missing information that would have helped make a definitive classification and categorized this information by ease and cost to obtain.Genet Med 19 1, 77-82.
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