<html><head><style>body{font-family:Helvetica,Arial;font-size:13px}</style></head><body style="word-wrap: break-word; -webkit-nbsp-mode: space; -webkit-line-break: after-white-space;"><div id="bloop_customfont" style="color: rgb(0, 0, 0); margin: 0px;"><font face="Helvetica">Hi,</font></div><div id="bloop_customfont" style="color: rgb(0, 0, 0); margin: 0px;"><font face="Helvetica"><br></font></div><div id="bloop_customfont" style="color: rgb(0, 0, 0); margin: 0px;"><font face="Helvetica">I’m annotating a variant using GRCh37 and the VEP in the v78 release and the HGVS annotation of the refseq transcripts doesn’t seem to match up to the sequences for those transcripts.</font></div><div id="bloop_customfont" style="color: rgb(0, 0, 0); margin: 0px;"><font face="Helvetica"><br></font></div><div id="bloop_customfont" style="margin: 0px;"><font face="Helvetica">The variant is in SLC37A4 (chr11:g.118895980CAG>C), the HGVS annotations are NM_001467.5:c.1043_1044delCT and NP_001458.1:p.Pro348ArgfsTer? and the amino acid is being annotated as CCT/C. The aa change is the same for all refseq transcripts in the annotation. </font></div><div id="bloop_customfont" style="margin: 0px;"><font face="Helvetica"><br></font></div><div id="bloop_customfont" style="margin: 0px;"><font face="Helvetica">The count seems to be off by one - it’s a CTG/G change. The local sequence context is GCC CTG TTT with the TG being deleted. </font></div><div id="bloop_customfont" style="color: rgb(0, 0, 0); margin: 0px;"><font face="Helvetica"><br></font></div><div id="bloop_customfont" style="color: rgb(0, 0, 0); margin: 0px;"><font face="Helvetica">The correct HGVS description is NM_001467.5:c.1042_1043delCT and the protein is <span style="color: rgb(51, 51, 51); line-height: 18px;">p.Leu348Valfs*53. This is annotated correctly in the Ensembl transcripts - </span>ENST00000545985.1:c.1042_1043delCT, ENSP00000475241.1:p.Leu348ValfsTer53. </font></div><div id="bloop_customfont" style="color: rgb(0, 0, 0); margin: 0px;"><font face="Helvetica"><br></font></div><div id="bloop_customfont" style="color: rgb(0, 0, 0); margin: 0px;"><font face="Helvetica">The following options were used for the annotation:</font></div><div id="bloop_customfont" style="color: rgb(0, 0, 0); margin: 0px;"><font face="Helvetica"><br></font></div><div id="bloop_customfont" style="color: rgb(0, 0, 0); margin: 0px;">—offline —everything —merged </div><div id="bloop_customfont" style="color: rgb(0, 0, 0); margin: 0px;"><br></div><div id="bloop_customfont" style="color: rgb(0, 0, 0); margin: 0px;">The same issue exists with the web version of VEP:</div><div id="bloop_customfont" style="color: rgb(0, 0, 0); margin: 0px;"><br></div><div id="bloop_customfont" style="color: rgb(0, 0, 0); margin: 0px;">http://grch37.ensembl.org/Homo_sapiens/Tools/VEP/Results?db=core;tl=Ba08mzoDSO2008gG-584627</div><div id="bloop_customfont" style="color: rgb(0, 0, 0); margin: 0px;"><br></div><div id="bloop_customfont" style="color: rgb(0, 0, 0); margin: 0px;"><br></div><div id="bloop_customfont" style="color: rgb(0, 0, 0); margin: 0px;">Thanks,</div><div id="bloop_customfont" style="color: rgb(0, 0, 0); margin: 0px;">Vasisht</div><font face="Helvetica"><br></font><div id="bloop_sign_1423003311172330752" class="bloop_sign"></div></body></html>