ArticleHuman mutation2008
Assessment of functional effects of unclassified genetic variants.
Article in Human mutation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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
47 citing papers in PubMed, 100 citations in OpenAlex.
- Combining multiplexed functional data to improve variant classification.Genome medicine · 2026Article
- Bayesian Integration of Tumor Mutational Signatures and Somatic Features Refines Pathogenicity Assessment of Germline Mismatch Repair Variants.Human mutation · 2026Article
- A Cell-Based Functional Assay Calibrated for Analysis ofHuman mutation · 2025Article
- Review
- Review
- Yeast-based assays for the functional characterization of cancer-associated variants of human DNA repair genes.Microbial cell (Graz, Austria) · 2020Review
- A Novel GermlineGenes · 2020Article
- Variants of uncertain significance in the era of high-throughput genome sequencing: a lesson from breast and ovary cancers.Journal of experimental & clinical cancer research : CR · 2020Review
- Quantifying the potential of functional evidence to reclassify variants of uncertain significance in the categorical and Bayesian interpretation frameworks.Human mutation · 2018Article
- Functional Interaction BetweenFrontiers in genetics · 2018Article
- Article
- Article
- Novel Implications in Molecular Diagnosis of Lynch Syndrome.Gastroenterology research and practice · 2017Review
- Functional Assessment of Genetic Variants with Outcomes Adapted to Clinical Decision-Making.PLoS genetics · 2016Article
- Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database.Nature genetics · 2014Article
- Gene variants of unknown clinical significance in Lynch syndrome. An introduction for clinicians.Familial cancer · 2013Article
- Calibration of multiple in silico tools for predicting pathogenicity of mismatch repair gene missense substitutions.Human mutation · 2013Article
- A classification model for BRCA2 DNA binding domain missense variants based on homology-directed repair activity.Cancer research · 2013Article
- Article
- Functional evaluation of BRCA2 variants mapping to the PALB2-binding and C-terminal DNA-binding domains using a mouse ES cell-based assay.Human molecular genetics · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 6 institutions in 3 countries.
Funding
Abstract
Inherited predisposition to disease is often linked to reduced activity of a disease associated gene product. Thus, quantitation of the influence of inherited variants on gene function can potentially be used to predict the disease relevance of these variants. While many disease genes have been extensively characterized at the functional level, few assays based on functional properties of the encoded proteins have been established for the purpose of predicting the contribution of rare inherited variants to disease. Much of the difficulty in establishing predictive functional assays stems from the technical complexity of the assays. However, perhaps the most challenging aspect of functional assay development for clinical testing purposes is the absolute requirement for validation of the sensitivity and specificity of the assays and the determination of positive predictive values (PPVs) and negative predictive values (NPVs) of the assays relative to a "gold standard" measure of disease predisposition. In this commentary, we provide examples of some of the functional assays under development for several cancer predisposition genes (BRCA1, BRCA2, CDKN2A, and mismatch repair [MMR] genes MLH1, MSH2, MSH6, and PMS2) and present a detailed review of the issues associated with functional assay development. We conclude that validation is paramount for all assays that will be used for clinical interpretation of inherited variants of any gene, but note that in certain circumstances information derived from incompletely validated assays may be valuable for classification of variants for clinical purposes when used to supplement data derived from other sources.
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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.