ArticleHuman mutation2018
Unique aspects of sequence variant interpretation for inborn errors of metabolism (IEM): The ClinGen IEM Working Group and the Phenylalanine Hydroxylase Gene.
Article in Human mutation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Chinese genetic variation database of inborn errors of metabolism: a systematic review of published variants in 13 genes.Orphanet journal of rare diseases · 2023Pooled it
- Comparative analysis of functional assay evidence use by ClinGen Variant Curation Expert Panels.Genome medicine · 2019Pooled it
- AAVC: An automated framework for high-accuracy ACMG-based variant classification.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
- Biochemical Testing Promotes Interpretation of Variants of Uncertain Significance in Prenatal Genetic Disease Testing in Four Organic Acidurias.Clinical genetics · 2026Review
- Article
- Assessing Allele Frequency Information: A Study of Variant Curation Expert Panel Guidelines.Human mutation · 2026Article
- Spectrum ofBiomedical reports · 2025Article
- Application of family whole-exome sequencing for prenatal diagnosis-an analysis of 357 cases.Frontiers in medicine · 2025Article
- Simultaneous CNV-seq and WES: An effective strategy for molecular diagnosis of unexplained fetal structural anomalies.Heliyon · 2024Article
- The PS4-likelihood ratio calculator: flexible allocation of evidence weighting for case-control data in variant classification.Journal of medical genetics · 2024Article
- Gene-specific ACMG/AMP classification criteria for germline APC variants: Recommendations from the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Quantitative thresholds for variant enrichment in 13,845 cases: improving pathogenicity classification in genetic hearing loss.Genome medicine · 2023Article
- Compilation of Genotype and Phenotype Data inGenes · 2023Article
- Specifications of the ACMG/AMP guidelines for ACADVL variant interpretation.Molecular genetics and metabolism · 2023Article
- DECIPHER: Improving Genetic Diagnosis Through Dynamic Integration of Genomic and Clinical Data.Annual review of genomics and human genetics · 2023Review
- Reasons and Resolutions for Inconsistent Variant Interpretation.Human mutation · 2023Review
- Systematic use of phenotype evidence in clinical genetic testing reduces the frequency of variants of uncertain significance.American journal of medical genetics. Part A · 2022Article
- Novel homozygous nonsense mutation associated with Bardet-Biedl syndrome in fetuses with congenital renal malformation.Medicine · 2022Article
- Identification of phenylketonuria patient genotypes using single-gene full-length sequencing.Human genomics · 2022Article
- Function of PHEX mutations p.Glu145* and p.Trp749Arg in families with X-linked hypophosphatemic rickets by the negative regulation mechanism on FGF23 promoter transcription.Cell death & disease · 2022Article
Corrections and comments
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Authors and funding
24 authors.
Funding
Abstract
The ClinGen Inborn Errors of Metabolism Working Group was tasked with creating a comprehensive, standardized knowledge base of genes and variants for metabolic diseases. Phenylalanine hydroxylase (PAH) deficiency was chosen to pilot development of the Working Group's standards and guidelines. A PAH variant curation expert panel (VCEP) was created to facilitate this process. Following ACMG-AMP variant interpretation guidelines, we present the development of these standards in the context of PAH variant curation and interpretation. Existing ACMG-AMP rules were adjusted based on disease (6) or strength (5) or both (2). Disease adjustments include allele frequency thresholds, functional assay thresholds, and phenotype-specific guidelines. Our validation of PAH-specific variant interpretation guidelines is presented using 85 variants. The PAH VCEP interpretations were concordant with existing interpretations in ClinVar for 69 variants (81%). Development of biocurator tools and standards are also described. Using the PAH-specific ACMG-AMP guidelines, 714 PAH variants have been curated and will be submitted to ClinVar. We also discuss strategies and challenges in applying ACMG-AMP guidelines to autosomal recessive metabolic disease, and the curation of variants in these genes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.