ArticleHuman mutation2008
In silico analysis of missense substitutions using sequence-alignment based methods.
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 112 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.
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.
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Who cites it
112 citing papers in PubMed, 197 citations in OpenAlex.
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- FAM20B Related Skeletal Dysplasia: Expanding the Prenatal Phenotype.Clinical genetics · 2026Article
- Identification of a novel missense mutation (L233Q) in the AMH gene in a polycystic ovary syndrome patient from Assam, India.Przeglad menopauzalny = Menopause review · 2026Article
- Leveraging in-silico deep learning and computational analyses to predict the pathogenicity of ROBO4 variants of uncertain significance in aortic aneurysm and dissection patients.BMC cardiovascular disorders · 2026Article
- Case Report: Association of a rare single nucleotide variant in the KCNH2 gene with drug-induced QT prolongation.Frontiers in genetics · 2026Article
- RAD50 missense variants differentially affect the DNA damage response and mitotic progression.FEBS letters · 2025Article
- Isolated Non-Progressive Hemidystonia in a Patient Homozygous for H63D Variant of Hereditary Hemochromatosis: A Case Report and Systematic Literature Review of Movement Disorders in Hereditary Hemochromatosis.Diagnostics (Basel, Switzerland) · 2025Article
- Classification of MLH1 Missense VUS Using Protein Structure-Based Deep Learning-Ramachandran Plot-Molecular Dynamics Simulations Method.International journal of molecular sciences · 2024Article
- Assembly and phylogeographical analysis of novel Taenia solium mitochondrial genomes suggest stratification within the African-American genotype.Parasites & vectors · 2023Article
- Integration of deep learning with Ramachandran plot molecular dynamics simulation for genetic variant classification.iScience · 2023Article
- Large scale genotype- and phenotype-driven machine learning in Von Hippel-Lindau disease.Human mutation · 2022Article
- Quantifying prediction of pathogenicity for within-codon concordance (PM5) using 7541 functional classifications of BRCA1 and MSH2 missense variants.Genetics in medicine : official journal of the American College of Medical Genetics · 2022Article
- Artificial Selection Drives SNPs of Olfactory Receptor Genes into Different Working Traits in Labrador Retrievers.Genetics research · 2022Article
- Analyzing Genetic Differences Between Sporadic Primary and Secondary/Tertiary Hyperparathyroidism by Targeted Next-Generation Panel Sequencing.Endocrine pathology · 2021Article
- Comprehensive Identification of DeleteriousInternational journal of molecular sciences · 2021Article
- Novel variants in the NARS2 gene as a cause of infantile-onset severe epilepsy leading to fatal refractory status epilepticus: case study and literature review.Neurogenetics · 2021Review
- Evolutionary and functional lessons from human-specific amino acid substitution matrices.NAR genomics and bioinformatics · 2021Article
- Clinical and Neuroimaging Features in Charcot-Marie-Tooth Patients withLife (Basel, Switzerland) · 2021Article
- Epidemiological and ES cell-based functional evaluation of BRCA2 variants identified in families with breast cancer.Human mutation · 2021Article
52 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Genetic testing for mutations in high-risk cancer susceptibility genes often reveals missense substitutions that are not easily classified as pathogenic or neutral. Among the methods that can help in their classification are computational analyses. Predictions of pathogenic vs. neutral, or the probability that a variant is pathogenic, can be made based on: 1) inferences from evolutionary conservation using protein multiple sequence alignments (PMSAs) of the gene of interest for almost any missense sequence variant; and 2) for many variants, structural features of wild-type and variant proteins. These in silico methods have improved considerably in recent years. In this work, we review and/or make suggestions with respect to: 1) the rationale for using in silico methods to help predict the consequences of missense variants; 2) important aspects of creating PMSAs that are informative for classification; 3) specific features of algorithms that have been used for classification of clinically-observed variants; 4) validation studies demonstrating that computational analyses can have predictive values (PVs) of approximately 75 to 95%; 5) current limitations of data sets and algorithms that need to be addressed to improve the computational classifiers; and 6) how in silico algorithms can be a part of the "integrated analysis" of multiple lines of evidence to help classify variants. We conclude that carefully validated computational algorithms, in the context of other evidence, can be an important tool for classification of missense variants.
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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.