ArticleHuman mutation2022
Predictive functional assay-based classification of PMS2 variants in Lynch syndrome.
Article in Human mutation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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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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Who cites it
9 citing papers in PubMed, 9 citations in OpenAlex.
- Analysis of structure and conservation for supporting functional evaluation of PMS2 missense variants.European journal of human genetics : EJHG · 2026Article
- Validation structures for sequence variants of uncertain significance in hereditary cancer.European journal of human genetics : EJHG · 2026Review
- Lynch Syndrome: An Update of Underlying Molecular Mechanisms, Phenotypes and Methods to Classify Variants of Uncertain Significance.Biomedicines · 2026Review
- An accurate cellular assay to determine pathogenicity of coding and noncoding variants in Lynch syndrome genes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Lynch Syndrome in Focus: A Multidisciplinary Review of Cancer Risk, Clinical Management, and Special Populations.Cancers · 2025Review
- Article
- A series of reviews in familial cancer: genetic cancer risk in context variants of uncertain significance in MMR genes: which procedures should be followed?Familial cancer · 2025Review
- Review
- Predictive functional assay-based classification of PMS2 variants in Lynch syndrome.Human mutation · 2022Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The large majority of germline alterations identified in the DNA mismatch repair (MMR) gene PMS2, a low-penetrance gene for the cancer predisposition Lynch syndrome, represent variants of uncertain significance (VUS). The inability to classify most VUS interferes with personalized healthcare. The complete in vitro MMR activity (CIMRA) assay, that only requires sequence information on the VUS, provides a functional analysis-based quantitative tool to improve the classification of VUS in MMR proteins. To derive a formula that translates CIMRA assay results into the odds of pathogenicity (OddsPath) for VUS in PMS2 we used a set of clinically classified PMS2 variants supplemented by inactivating variants that were generated by an in cellulo genetic screen, as proxies for cancer-predisposing variants. Validation of this OddsPath revealed high predictive values for benign and predisposing PMS2 VUS. We conclude that the OddsPath provides an integral metric that, following the other, higher penetrance, MMR proteins MSH2, MSH6 and MLH1 can be incorporated as strong evidence type into the upcoming criteria for MMR gene VUS classification of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP).
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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.