ArticleHuman mutation2013
Calibration of multiple in silico tools for predicting pathogenicity of mismatch repair gene missense substitutions.
Article in Human mutation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
56 citing papers in PubMed, 92 citations in OpenAlex.
- Analysis of structure and conservation for supporting functional evaluation of PMS2 missense variants.European journal of human genetics : EJHG · 2026Article
- The Tyrolean FounderBiomolecules · 2026Article
- Population frequency of Predicted pathogenic MisMatch Repair (MMR) gene variants in Lynch syndrome from bioinformatic analyses of the general population.Scientific reports · 2025Article
- Multi-class machine learning-based classification of SCID-related genetic variants.Immunologic research · 2025Article
- Meta-EA: a gene-specific combination of available computational tools for predicting missense variant effects.Nature communications · 2025Article
- Reclassification of Two MLH1 Variants of Uncertain Significance Utilizing Clinical and Functional Data.Molecular genetics & genomic medicine · 2024Article
- Insights from the SNP analysis of TYMP gene linking MNGIE.Bioinformation · 2024Article
- Article
- Rare single-nucleotide variants of MLH1 and MSH2 genes in patients with Lynch syndrome.Cancer reports (Hoboken, N.J.) · 2024Article
- Constitutional mismatch repair deficiency syndrome with atypical features caused by a homozygousFrontiers in oncology · 2023Article
- Predictive functional assay-based classification of PMS2 variants in Lynch syndrome.Human mutation · 2022Article
- Comprehensive evaluation and efficient classification of BRCA1 RING domain missense substitutions.American journal of human genetics · 2022Article
- Interpreting protein variant effects with computational predictors and deep mutational scanning.Disease models & mechanisms · 2022Review
- Induction of mismatch repair deficiency, compromised DNA damage signaling and compound hypermutagenesis by a dietary mutagen in a cell-based model for Lynch syndrome.Carcinogenesis · 2022Article
- Functional characterization of MLH1 missense variants unveils mechanisms of pathogenicity and clarifies role in cancer.PloS one · 2022Article
- Variants of uncertain clinical significance in hereditary breast and ovarian cancer genes: best practices in functional analysis for clinical annotation.Journal of medical genetics · 2020Review
- Contribution of mRNA Splicing to Mismatch Repair Gene Sequence Variant Interpretation.Frontiers in genetics · 2020Article
- Curated multiple sequence alignment for the Adenomatous Polyposis Coli (APC) gene and accuracy of in silico pathogenicity predictions.PloS one · 2020Article
- Targeted sequencing of genes associated with the mismatch repair pathway in patients with endometrial cancer.PloS one · 2020Article
- Functional interrogation of Lynch syndrome-associated MSH2 missense variants via CRISPR-Cas9 gene editing in human embryonic stem cells.Human mutation · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 13 institutions in 4 countries.
Funding
Abstract
Classification of rare missense substitutions observed during genetic testing for patient management is a considerable problem in clinical genetics. The Bayesian integrated evaluation of unclassified variants is a solution originally developed for BRCA1/2. Here, we take a step toward an analogous system for the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) that confer colon cancer susceptibility in Lynch syndrome by calibrating in silico tools to estimate prior probabilities of pathogenicity for MMR gene missense substitutions. A qualitative five-class classification system was developed and applied to 143 MMR missense variants. This identified 74 missense substitutions suitable for calibration. These substitutions were scored using six different in silico tools (Align-Grantham Variation Grantham Deviation, multivariate analysis of protein polymorphisms [MAPP], MutPred, PolyPhen-2.1, Sorting Intolerant From Tolerant, and Xvar), using curated MMR multiple sequence alignments where possible. The output from each tool was calibrated by regression against the classifications of the 74 missense substitutions; these calibrated outputs are interpretable as prior probabilities of pathogenicity. MAPP was the most accurate tool and MAPP + PolyPhen-2.1 provided the best-combined model (R(2) = 0.62 and area under receiver operating characteristic = 0.93). The MAPP + PolyPhen-2.1 output is sufficiently predictive to feed as a continuous variable into the quantitative Bayesian integrated evaluation for clinical classification of MMR gene missense substitutions.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.