ArticleHuman mutation2013
A multifactorial likelihood model for MMR gene variant classification incorporating probabilities based on sequence bioinformatics and tumor characteristics: a report from the Colon Cancer Family Registry.
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 48 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
48 citing papers in PubMed.
- Validation structures for sequence variants of uncertain significance in hereditary cancer.European journal of human genetics : EJHG · 2026Review
- Analysis of structure and conservation for supporting functional evaluation of PMS2 missense variants.European journal of human genetics : EJHG · 2026Article
- The Tyrolean FounderBiomolecules · 2026Article
- Integrating breast tumour homologous recombination deficiency status to aid germline BRCA1 and BRCA2 variant classification.EBioMedicine · 2026Article
- Bayesian Integration of Tumor Mutational Signatures and Somatic Features Refines Pathogenicity Assessment of Germline Mismatch Repair Variants.Human mutation · 2026Article
- Misclassification of a frequent variant from PMS2CL pseudogene as a PMS2 loss of function variant in Brazilian patients.Familial cancer · 2024Article
- Case report: Exploring Lynch Syndrome through genomic analysis in a mestizo Ecuadorian patient and his brother.Frontiers in medicine · 2024Article
- Article
- A calibrated cell-based functional assay to aid classification of MLH1 DNA mismatch repair gene variants.Human mutation · 2022Article
- Identifying colorectal cancer caused by biallelic MUTYH pathogenic variants using tumor mutational signatures.Nature communications · 2022Article
- Multiplexing mutation rate assessment: determining pathogenicity of Msh2 variants in Saccharomyces cerevisiae.Genetics · 2021Article
- Identification of a novel pathogenic MLH1 mutation and recommended genetic screening strategy: An investigation of three Chinese Lynch syndrome pedigrees.Molecular genetics & genomic medicine · 2020Article
- Comprehensive Constitutional Genetic and Epigenetic Characterization of Lynch-Like Individuals.Cancers · 2020Article
- Contribution of mRNA Splicing to Mismatch Repair Gene Sequence Variant Interpretation.Frontiers in genetics · 2020Article
- Lynch syndrome with exclusive skin involvement: time to consider a molecular definition?Familial cancer · 2019Article
- Radiomics based likelihood functions for cancer diagnosis.Scientific reports · 2019Article
- Lessons learned from two decades of BRCA1 and BRCA2 genetic testing: the evolution of data sharing and variant classification.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Review
- A functional assay-based procedure to classify mismatch repair gene variants in Lynch syndrome.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Article
- Outcomes of 92 patient-driven family studies for reclassification of variants of uncertain significance.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Article
- Genetic predisposition to colorectal cancer: syndromes, genes, classification of genetic variants and implications for precision medicine.The Journal of pathology · 2019Review
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.
Funding
Abstract
Mismatch repair (MMR) gene sequence variants of uncertain clinical significance are often identified in suspected Lynch syndrome families, and this constitutes a challenge for both researchers and clinicians. Multifactorial likelihood model approaches provide a quantitative measure of MMR variant pathogenicity, but first require input of likelihood ratios (LRs) for different MMR variation-associated characteristics from appropriate, well-characterized reference datasets. Microsatellite instability (MSI) and somatic BRAF tumor data for unselected colorectal cancer probands of known pathogenic variant status were used to derive LRs for tumor characteristics using the Colon Cancer Family Registry (CFR) resource. These tumor LRs were combined with variant segregation within families, and estimates of prior probability of pathogenicity based on sequence conservation and position, to analyze 44 unclassified variants identified initially in Australasian Colon CFR families. In addition, in vitro splicing analyses were conducted on the subset of variants based on bioinformatic splicing predictions. The LR in favor of pathogenicity was estimated to be ~12-fold for a colorectal tumor with a BRAF mutation-negative MSI-H phenotype. For 31 of the 44 variants, the posterior probabilities of pathogenicity were such that altered clinical management would be indicated. Our findings provide a working multifactorial likelihood model for classification that carefully considers mode of ascertainment for gene testing.
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.