GuidelineGenetics in medicine : official journal of the American College of Medical Genetics2018
ClinGen's RASopathy Expert Panel consensus methods for variant interpretation.
Guideline in Genetics in medicine : official journal of the American College of Medical Genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 3 of them syntheses that pooled it.
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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
107 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Is It Feasible to Screen for Fetal De Novo or Paternally Inherited Pathogenic Single Nucleotide Variants in Maternal Plasma Cell-Free DNA? A Systematic Literature Review.Prenatal diagnosis · 2025Pooled it
- Cancer in Costello syndrome: a systematic review and meta-analysis.British journal of cancer · 2023Pooled it
- Comparative analysis of functional assay evidence use by ClinGen Variant Curation Expert Panels.Genome medicine · 2019Pooled it
- Global Recommendations for the Use of Diagnostic Genomic Sequencing in the Prenatal Setting on Behalf of the ESHG and ISPD.Prenatal diagnosis · 2026Article
- Global recommendations for the use of diagnostic genomic sequencing in the prenatal setting on behalf of the ESHG and ISPD.European journal of human genetics : EJHG · 2026Article
- BiallelicJournal of neuromuscular diseases · 2026Article
- ACMG/AMP variant classification specifications from the ClinGen Epilepsy Sodium Channel Variant Curation Expert Panel.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
- AAVC: An automated framework for high-accuracy ACMG-based variant classification.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
- Genetic spectrum and clinical features of PMP22 point mutations in Japanese Charcot-Marie-Tooth disease.Journal of neurology · 2026Article
- Genotype-Phenotype Analysis and New Clinical Findings in a Series of 24 Patients Presenting with Noonan Syndrome and Related Disorders.Molecular syndromology · 2026Article
- Article
- Assessing Allele Frequency Information: A Study of Variant Curation Expert Panel Guidelines.Human mutation · 2026Article
- Correcting PVS1 overestimation: clinical insights into rescue transcripts and variant reclassification in 4 prenatal cases.Frontiers in medicine · 2026Article
- Expanding the Genetic Landscape of RASopathies: Significance of IncludingMolecular syndromology · 2025Article
- Molecular and Clinical Profiles of Patients with RASopathies: Targeted Next-Generation Sequencing Panel Results and Identification of 14 Novel Disease-Causing Variants.Molecular syndromology · 2025Article
- Charcot-Marie-Tooth-like presentation in giant axonal neuropathy: clinical variability and prevalence in a large Japanese case series.Journal of neurology · 2025Article
- Conserved missense variant pathogenicity and correlated phenotypes across paralogous genes.Genome biology · 2025Article
- A literature review and pooled case analysis of cardiofaciocutaneous syndrome to estimate cancer risk.Genetics in medicine : official journal of the American College of Medical Genetics · 2025Review
- Neurofibromatosis-Noonan syndrome: a prospective monocentric study of 26 patients and literature review.Orphanet journal of rare diseases · 2025Review
- Genetic landscape in undiagnosed patients with syndromic hearing loss revealed by whole exome sequencing and phenotype similarity search.Human genetics · 2025Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
purposeStandardized and accurate variant assessment is essential for effective medical care. To that end, Clinical Genome (ClinGen) Resource clinical domain working groups (CDWGs) are systematically reviewing disease-associated genes for sufficient evidence to support disease causality and creating disease-specific specifications of American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG-AMP) guidelines for consistent and accurate variant classification.
methodsThe ClinGen RASopathy CDWG established an expert panel to curate gene information and generate gene- and disease-specific specifications to ACMG-AMP variant classification framework. These specifications were tested by classifying 37 exemplar pathogenic variants plus an additional 66 variants in ClinVar distributed across nine RASopathy genes.
resultsRASopathy-related specifications were applied to 16 ACMG-AMP criteria, with 5 also having adjustable strength with availability of additional evidence. Another 5 criteria were deemed not applicable. Key adjustments to minor allele frequency thresholds, multiple de novo occurrence events and/or segregation, and strength adjustments impacted 60% of variant classifications. Unpublished case-level data from participating laboratories impacted 45% of classifications supporting the need for data sharing.
conclusionRAS-specific ACMG-AMP specifications optimized the utility of available clinical evidence and Ras/MAPK pathway-specific characteristics to consistently classify RASopathy-associated variants. These specifications highlight how grouping genes by shared features promotes rapid multigenic variant assessment without sacrificing specificity and accuracy.
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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.