{"id":4410,"date":"2018-02-04T21:03:55","date_gmt":"2018-02-04T21:03:55","guid":{"rendered":"http:\/\/www.cytognomix.com\/?p=4410"},"modified":"2018-02-04T21:03:55","modified_gmt":"2018-02-04T21:03:55","slug":"dec-7-2017-rogan-pk-mucaki-ej-comment-on-pmid-29185120-characterization-of-a-novel-germline-brca1-splice-variant-c-53324dela-in-pubmed-commons-internet-bethesda-md-national-library-of","status":"publish","type":"post","link":"https:\/\/www.cytognomix.com\/?p=4410","title":{"rendered":"Dec. 7, 2017. Rogan PK, Mucaki EJ. Comment on PMID 29185120: Characterization of a novel germline BRCA1 splice variant, c.5332+4delA. In: PubMed Commons [Internet]. Bethesda (MD): National Library of Medicine; 2017 Nov 28 [cited 2017 Dec 7]."},"content":{"rendered":"<p><a id=\"ui-ncbipopper-9\" role=\"button\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/myncbi\/peter.rogan.1\/comments\/\" class=\"broken_link\">Peter Rogan<\/a><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/29185120#cm29185120_77962\">2017 Dec 07 5:24 p.m.<\/a><\/p>\n<div data-md=\"We have analyzed this mutation with the Automated Splice Site and Exon Definition Analysis server (ASSEDA). The 1 nt deletion in the splice donor of exon 20 reduces the strength of this site from 11.5 -&gt; 4.1 bits.  (100\/[2^7.4 bits] = 0.6% binding affinity)\n\nThe information theory-based approach used in ASSEDA predicts isoform abundance and computes the fold changes in binding affinity from mutations (&lt;PMID:23348723&gt;), which corresponds to the degree of exon skipping in this case. The reduction in splice site strength is much greater than the estimates given by the ad hoc methods used in the paper. LOH was not complete; some of the observed expression may have been derived from the contaminating normal allele. In fact, had the loss of function in splice site recognition only been 25-40% according to the paper, it could have been classified as a variant of unknown significance, or possibly as benign (as we suggested in &lt;PMID:21523855&gt;).\"><\/p>\n<p>We have analyzed this mutation with the Automated Splice Site and Exon Definition Analysis server (ASSEDA). The 1 nt deletion in the splice donor of exon 20 reduces the strength of this site from 11.5 -&gt; 4.1 bits. (100\/[27.4\u00a0bits] = 0.6% binding affinity)<\/p>\n<p>The information theory-based approach used in ASSEDA predicts isoform abundance and computes the fold changes in binding affinity from mutations (<a title=\"Prediction of mutant mRNA splice isoforms by information theory-based exon definition.\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23348723\/\">Mucaki EJ, 2013<\/a>), which corresponds to the degree of exon skipping in this case. The reduction in splice site strength is much greater than the estimates given by the ad hoc methods used in the paper. LOH was not complete; some of the observed expression may have been derived from the contaminating normal allele. In fact, had the loss of function in splice site recognition only been 25-40% according to the paper, it could have been classified as a variant of unknown significance, or possibly as benign (as we suggested in\u00a0<a title=\"Comprehensive prediction of mRNA splicing effects of BRCA1 and BRCA2 variants.\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/21523855\/\">Mucaki EJ, 2011<\/a>).<\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Peter Rogan2017 Dec 07 5:24 p.m. We have analyzed this mutation with the Automated Splice Site and Exon Definition Analysis server (ASSEDA). The 1 nt deletion in the splice donor of exon 20 reduces the strength of this site from 11.5 -&gt; 4.1 bits. (100\/[27.4\u00a0bits] = 0.6% binding affinity) The information theory-based approach used in [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[6],"tags":[],"_links":{"self":[{"href":"https:\/\/www.cytognomix.com\/index.php?rest_route=\/wp\/v2\/posts\/4410"}],"collection":[{"href":"https:\/\/www.cytognomix.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.cytognomix.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.cytognomix.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.cytognomix.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=4410"}],"version-history":[{"count":1,"href":"https:\/\/www.cytognomix.com\/index.php?rest_route=\/wp\/v2\/posts\/4410\/revisions"}],"predecessor-version":[{"id":4411,"href":"https:\/\/www.cytognomix.com\/index.php?rest_route=\/wp\/v2\/posts\/4410\/revisions\/4411"}],"wp:attachment":[{"href":"https:\/\/www.cytognomix.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=4410"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.cytognomix.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=4410"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.cytognomix.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=4410"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}