<div dir="ltr">Hi-<div><br></div><div>VEP 2.8 and VEP 71 appear to have a bug in which the start coordinate for protein HGVSp effects are repeated for certain delins variants.</div><div><br></div><div><div>For example, with this VCF line as input:</div>

<div>  3<span class="" style="white-space:pre"> </span>10191482<span class="" style="white-space:pre">  </span>CVID1003553<span class="" style="white-space:pre">       </span>A<span class="" style="white-space:pre"> </span>ATTT<span class="" style="white-space:pre">      </span>60<span class="" style="white-space:pre">        </span>PASS</div>

<div>VEP 2.3 correctly returns <br></div><div><div><div>  HGVSp=ENSP00000256474.2:p.Lys159delinsIleX</div><div>  HGVSp=ENSP00000344757.2:p.Lys118delinsIleX</div><div>for two transcripts, whereas VEP 2.8 and VEP 71 each return</div>

</div></div></div><div style>  HGVSp=ENSP00000256474.2:p.Lys159159delinsIleX<br></div><div style><div>  HGVSp=ENSP00000344757.2:p.Lys118118delinsIleX</div><div style>(two coding transcripts)</div><div><br></div></div><div style>

Notice that the start coordinates, 159 and 118, are repeated VEP 2.8 and 71.</div><div style><br></div><div style><br></div><div style>More examples:</div><div style><div>5<span class="" style="white-space:pre"> </span>112175315<span class="" style="white-space:pre"> </span>CVID1010109<span class="" style="white-space:pre">       </span>T<span class="" style="white-space:pre"> </span>TAAA<span class="" style="white-space:pre">      </span>60<span class="" style="white-space:pre">        </span>PASS<br>

</div><div>9<span class="" style="white-space:pre">       </span>98238379<span class="" style="white-space:pre">  </span>CVID6007616<span class="" style="white-space:pre">       </span>AT<span class="" style="white-space:pre">        </span>ACTGCTGC<span class="" style="white-space:pre">  </span>60<span class="" style="white-space:pre">        </span>PASS</div>

<div>10<span class="" style="white-space:pre">  </span>43610045<span class="" style="white-space:pre">  </span>CVID4000412<span class="" style="white-space:pre">       </span>AG<span class="" style="white-space:pre">        </span>ATTCT<span class="" style="white-space:pre">     </span>60<span class="" style="white-space:pre">        </span>PASS</div>

<div>10<span class="" style="white-space:pre">  </span>89711990<span class="" style="white-space:pre">  </span>CVID4000640<span class="" style="white-space:pre">       </span>TTCC<span class="" style="white-space:pre">      </span>TATAAAT<span class="" style="white-space:pre">   </span>60<span class="" style="white-space:pre">        </span>PASS</div>

<div>17<span class="" style="white-space:pre">  </span>7578202<span class="" style="white-space:pre">   </span>CVID6007473<span class="" style="white-space:pre">       </span>AC<span class="" style="white-space:pre">        </span>AACCA<span class="" style="white-space:pre">     </span>60<span class="" style="white-space:pre">        </span>PASS</div>

<div>17<span class="" style="white-space:pre">  </span>78063675<span class="" style="white-space:pre">  </span>CVID6004403<span class="" style="white-space:pre">       </span>A<span class="" style="white-space:pre"> </span>ATGT<span class="" style="white-space:pre">      </span>60<span class="" style="white-space:pre">        </span>PASS</div>

<div><br></div></div><div style><br></div><div style>The error appears to be in TranscriptVariationAllele.pm:794:<br></div><div><br></div>
<div>$hgvs_notation->{'hgvs'} .= $ref_pep_first . $hgvs_notation->{start} . $hgvs_notation->{end} . $hgvs_notation->{type} . $hgvs_notation->{alt} ;<br></div><div><br></div><div style>Having both $ref_pep_first and $hgvs_notation->{start} has the effect of repeating the starting coordinate. Removing $hgvs_notation->{start} from the above line solves this problem for these cases, but I'm unsure that I fully understand the logic that is implemented in _get_hgvs_protein_format or the impact of this change on other cases.<br>

</div><div><br></div><div><br></div><div style>-Reece</div><div style><br></div></div>