A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2017; you can also visit the original URL.
The file type is application/pdf.
Filters
Towards Increasing the Clinical Relevance of In Silico Methods to Predict Pathogenic Missense Variants
2016
PLoS Computational Biology
Preserved Fulltext
The need to interpret these variants continues to motivate development of better in silico bioinformatic methods. ...
Despite the development of dozens of such methods over the past 15 years, clinically relevant prediction accuracy remains elusive. ...
enable development of new in silico bioinformatics methods to predict variant impact on endophenotypes. ...
doi:10.1371/journal.pcbi.1004725
pmid:27171182
pmcid:PMC4865359
fatcat:xdzpensdovdv3fvo3jjddg3opq
Performance of in silico prediction tools for the classification of rare BRCA1/2 missense variants in clinical diagnostics
2018
BMC Medical Genomics
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2018; you can also visit the original URL.
The file type is application/pdf.
Conclusion: We show that due to low specificities state-of-the-art in silico prediction tools are not suitable to predict pathogenicity of variants of uncertain significance in BRCA1/2. ...
The use of next-generation sequencing approaches in clinical diagnostics has led to a tremendous increase in data and a vast number of variants of uncertain significance that require interpretation. ...
Acknowledgements The authors thank the German Cancer Aid (grant number 110837) for funding and Sandra Schmidt (Center for Familial Breast and Ovarian Cancer, Cologne) for excellent technical assistance ...
doi:10.1186/s12920-018-0353-y
pmid:29580235
pmcid:PMC5870501
fatcat:ylcngnnmzrgqtde4p33qf3uqsm
Assessing performance of pathogenicity predictors using clinically-relevant variant datasets
[article]
2020
biorxiv/medrxiv
pre-print
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2021; you can also visit the original URL.
The file type is application/pdf.
Purpose: Pathogenicity predictors are an integral part of genomic variant interpretation but, despite their widespread usage, an independent validation of performance using a clinically-relevant dataset ...
Results: Although the newer meta-predictors outperform the older tools, the performance of all pathogenicity predictors is substantially lower in the clinically-representative dataset. ...
Acknowledgements We wish to thank all the patients and family members who participated in the study. We also thank Dr ...
doi:10.1101/2020.02.06.937169
fatcat:pmq2xqmsu5caha4wuantc3lvsa
Assessing performance of pathogenicity predictors using clinically relevant variant datasets
2020
Journal of Medical Genetics
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2020; you can also visit the original URL.
The file type is application/pdf.
2.ResultsAlthough the newer meta-predictors outperform the older tools, the performance of all pathogenicity predictors is substantially lower in the clinically representative dataset. ...
BackgroundPathogenicity predictors are integral to genomic variant interpretation but, despite their widespread usage, an independent validation of performance using a clinically relevant dataset has not ...
Acknowledgements We wish to thank all the patients and family members who participated in the study. ...
doi:10.1136/jmedgenet-2020-107003
pmid:32843488
pmcid:PMC8327323
fatcat:p5arsgtt7janffoj2lgfl6almu
Using structural analysis to assess the impact of missense variants in MEN1
[article]
2019
bioRxiv
pre-print
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2020; you can also visit the original URL.
The file type is application/pdf.
variants with existing sequence- and conservation-based approaches can provide increased specificity in assessing the impact of missense variants in MEN1 in a clinical setting. ...
ABSTRACTPurposeThermodynamic analysis of protein structure in silico has been shown to be effective in discriminating between the effects of benign and pathogenic variation in the MSH2 protein. ...
For these reasons, methods to assist the classification of variants in MEN1 would be of clinical value. ...
doi:10.1101/661512
fatcat:r5n7ahlmpfab5leluyzscnsipu
Using structural analysis in silico to assess the impact of missense variants in MEN1
2019
Journal of the Endocrine Society
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2021; you can also visit the original URL.
The file type is application/pdf.
Previous studies have shown that thermodynamic analysis of protein structure in silico can discriminate between groups of benign and pathogenic missense variants. ...
Subsequent analysis of 7 novel missense variants identified during clinical testing of MEN1 patients showed that all 7 were predicted to destabilise menin by >4 kcal/mol. ...
subsequently used to calculate average values for each variant [38] . ...
doi:10.1210/js.2019-00260
pmid:31737856
pmcid:PMC6846327
fatcat:ohkpwnu2irh5heeyevcvdwqox4
Calibration of Multiple In Silico Tools for Predicting Pathogenicity of Mismatch Repair Gene Missense Substitutions
2012
Human Mutation
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2019; you can also visit the original URL.
The file type is application/pdf.
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 ...
to estimate prior probabilities of pathogenicity for MMR gene missense substitutions. ...
Acknowledgments For helpful discussions in refining the qualitative criteria that were used for qualitative classification of missense variants in this study, we thank the other members of the InSiGHT ...
doi:10.1002/humu.22214
pmid:22949387
pmcid:PMC4318556
fatcat:5m7wonq3tnbxdeabjnpzuq427m
Multimodal Analysis of SCN1A Missense Variants Improves Interpretation of Clinically Relevant Variants in Dravet Syndrome
2019
Frontiers in Neurology
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2020; you can also visit the original URL.
The file type is application/pdf.
Methods: We established a score classification workflow based on evidence of pathogenicity to adapt the classification of DS-related SCN1A missense variants. ...
Objective: We aimed to improve the classification of SCN1A missense variants in patients with Dravet syndrome (DS) by combining and modifying the current variants classification criteria to minimize inconclusive ...
ACKNOWLEDGMENTS We gratefully acknowledge the patients and their families for participating in this study. ...
doi:10.3389/fneur.2019.00289
pmid:31001185
pmcid:PMC6455056
fatcat:dfexqmqufnbrbaruhjdnlbfpwm
Enhanced prediction of gene and missense rare-variant pathogenicity by joint analysis of gene burden and amino-acid residue position
[article]
2019
bioRxiv
pre-print
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2020; you can also visit the original URL.
The file type is application/pdf.
Although rare missense variants underlying a number of Mendelian diseases have been noted to cluster in specific regions of proteins, this information may be underutilized when evaluating the pathogenicity ...
In conclusion, the inclusion of amino-acid residue positional information enhances the accuracy of gene and rare variant pathogenicity interpretation. ...
Acknowledgements We would like to acknowledge Anuj Goel for his bioinformatics support in data curation and Michael Bowman for his support in accessing data from the clinical genetics laboratory. ...
doi:10.1101/826164
fatcat:366d5vqkajdiditsqivyf5yhte
Assessing Lysosomal Disorders in the NGS Era: Identification of Novel Rare Variants
2020
International Journal of Molecular Sciences
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2020; you can also visit the original URL.
The file type is application/pdf.
One of the novel pathogenic variants was identified in the GM2A gene, which is associated with an ultra-rare (or misdiagnosed) LSD, the AB variant of GM2 Gangliosidosis. ...
Importantly, four of those variants were novel, and, when applicable, their effect over protein structure was evaluated through in silico analysis. ...
Acknowledgments: The authors are grateful to the patients, families and also to all colleagues who provided them valuable information. We also thank to the Facility of Sequencing, INSA. ...
doi:10.3390/ijms21176355
pmid:32883051
fatcat:2w5sqhchcfcjfihuo5dtfqjo4e
Dissecting in silico Mutation Prediction of Variants in African Genomes: Challenges and Perspectives
2019
Frontiers in Genetics
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2020; you can also visit the original URL.
The file type is application/pdf.
However, the variability in the in silico prediction methods and categorization of functionally relevant genetic variants can pose specific challenges in some populations. ...
Genomic medicine is set to drastically improve clinical care globally due to high throughput technologies which enable speedy in silico detection and analysis of clinically relevant mutations. ...
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ...
doi:10.3389/fgene.2019.00601
pmid:31293624
pmcid:PMC6603221
fatcat:53hsn6g5nvdn3jcaaw3revkzfm
Specifications of the ACMG/AMP variant curation guidelines for the analysis of germline CDH1 sequence variants
2018
Human Mutation
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2020; you can also visit the original URL.
The file type is application/pdf.
framework to assess variant pathogenicity; however, these rules are not genespecific. ...
Overall, the ClinGen CDH1 VCEP recommends the use of these CDH1-specific guidelines for the assessment and classification of variants identified in this clinically actionable gene. ...
of the Hereditary Cancer Clinical Domain Working Group for their experience and guidance in developing these rule specifications. ...
doi:10.1002/humu.23650
pmid:30311375
pmcid:PMC6188664
fatcat:atmxyuxg5nhi3bnzq2fwobfmla
A functional assay–based procedure to classify mismatch repair gene variants in Lynch syndrome
2018
Genetics in Medicine
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2021; you can also visit the original URL.
The file type is application/pdf.
To enhance classification of variants of uncertain significance (VUS) in the DNA mismatch repair (MMR) genes in the cancer predisposition Lynch syndrome, we developed the cell-free in vitro MMR activity ...
Here, we calibrate and validate the assay, enabling its integration with in silico and clinical data. ...
Bayesian integration of cell-free in vitro MMR activity (CIMRA) assay values and in silico predictions of pathogenicity correctly classifies~90% of missense variants. ...
doi:10.1038/s41436-018-0372-2
pmid:30504929
pmcid:PMC7901556
fatcat:gl37kzkt4jbivjhs33s5svuecq
Pathogenicity Interpretation in the Age of Precision Medicine: The 2015 Annual Scientific Meeting of the Human Genome Variation Society
2016
Human Mutation
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2017; you can also visit the original URL.
The file type is application/pdf.
The authors would like to thank the speakers for their help in the preparation of this report. This meeting was run in partnership with The Human Variome Project. Dr. ...
Acknowledgments The Scientific Program Committee would like to thank Rania Horaitis, Heather Howard, and Timothy Smith for their professional help in running the HGVS Annual Meeting. ...
In silico prediction of variant pathogenicity has the potential to be clinically important but there are weaknesses in the current paradigm. ...
doi:10.1002/humu.22958
pmid:26791113
pmcid:PMC4783187
fatcat:bybttx64drft5dqeeolelicu3m
Medical genomics: The intricate path from genetic variant identification to clinical interpretation
2014
Applied and Translational Genomics
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2017; you can also visit the original URL.
The file type is application/pdf.
The field of medical genomics involves translating high throughput genetic methods to the clinic, in order to improve diagnostic efficiency and treatment decision making. ...
There is no single piece of evidence enough on its own to make firm conclusions on the pathogenicity and disease causality of a given variant. ...
Patricia Blanco for fruitful discussions on variant interpretation and clinical reporting, as well as to Dr. Jorge Amigo for bioinformatics support. ...
doi:10.1016/j.atg.2014.06.001
pmid:27284505
pmcid:PMC4887840
fatcat:d6s27q3aijh3tf34wpqkrfdfx4
« Previous
Showing results 1 — 15 out of 2,322 results