Please use this identifier to cite or link to this item: https://doi.org/10.1038/gim.2016.90
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dc.titleReassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples
dc.contributor.authorWalsh R.
dc.contributor.authorThomson K.L.
dc.contributor.authorWare J.S.
dc.contributor.authorFunke B.H.
dc.contributor.authorWoodley J.
dc.contributor.authorMcGuire K.J.
dc.contributor.authorMazzarotto F.
dc.contributor.authorBlair E.
dc.contributor.authorSeller A.
dc.contributor.authorTaylor J.C.
dc.contributor.authorMinikel E.V.
dc.contributor.authorMacArthur D.G.
dc.contributor.authorFarrall M.
dc.contributor.authorCook S.A.
dc.contributor.authorWatkins H.
dc.date.accessioned2019-01-08T09:07:46Z
dc.date.available2019-01-08T09:07:46Z
dc.date.issued2017
dc.identifier.citationWalsh R., Thomson K.L., Ware J.S., Funke B.H., Woodley J., McGuire K.J., Mazzarotto F., Blair E., Seller A., Taylor J.C., Minikel E.V., MacArthur D.G., Farrall M., Cook S.A., Watkins H. (2017). Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. Genetics in Medicine 19 (2) : 192-203. ScholarBank@NUS Repository. https://doi.org/10.1038/gim.2016.90
dc.identifier.issn10983600
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/150638
dc.description.abstractPurpose:The accurate interpretation of variation in Mendelian disease genes has lagged behind data generation as sequencing has become increasingly accessible. Ongoing large sequencing efforts present huge interpretive challenges, but they also provide an invaluable opportunity to characterize the spectrum and importance of rare variation.Methods:We analyzed sequence data from 7,855 clinical cardiomyopathy cases and 60,706 Exome Aggregation Consortium (ExAC) reference samples to obtain a better understanding of genetic variation in a representative autosomal dominant disorder.Results:We found that in some genes previously reported as important causes of a given cardiomyopathy, rare variation is not clinically informative because there is an unacceptably high likelihood of false-positive interpretation. By contrast, in other genes, we find that diagnostic laboratories may be overly conservative when assessing variant pathogenicity.Conclusions:We outline improved analytical approaches that evaluate which genes and variant classes are interpretable and propose that these will increase the clinical utility of testing across a range of Mendelian diseases. © American College of Medical Genetics and Genomics.
dc.publisherNature Publishing Group
dc.sourceScopus
dc.subjectClinical genetics
dc.subjectExome Aggregation Consortium
dc.subjectInherited cardiomyopathy
dc.subjectMendelian genetics
dc.subjectVariation interpretation
dc.typeArticle
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1038/gim.2016.90
dc.description.sourcetitleGenetics in Medicine
dc.description.volume19
dc.description.issue2
dc.description.page192-203
dc.description.codenGEMEF
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