Hi Michael,<div><br></div><div>This is indeed a bug in the HGVS nomenclature generation. I've committed a fix to the CVS so if you download a new version of the ensembl-variation/modules/Bio/EnsEMBL/Variation/VariationFeature.pm module (from head or ensembl-branch-63 code) and replace your existing module with it, the output should be correct. In your specific example - as you point out - the mutation is "silent" w.r.t. the protein so the HGVS notation should not indicate it as an insertion.</div>
<meta charset="utf-8"><div><br></div><div>Many thanks for reporting this and apologies for any inconvenience.</div><div>/Pontus Larsson - Ensembl Variation </div><div><br><br><div class="gmail_quote">2011/8/4 Michael Yourshaw <span dir="ltr"><<a href="mailto:myourshaw@ucla.edu">myourshaw@ucla.edu</a>></span><br>
<blockquote class="gmail_quote" style="margin:0 0 0 .8ex;border-left:1px #ccc solid;padding-left:1ex;"><div style="word-wrap:break-word">I get this error on some VCF files with the Variant Effect Predictor. It seems to be caused by an anomaly in the VariationFeature hgvs_notation code when an insert follows a stop codon (and maybe in other cases?).<div>
<br></div><div><div>substr outside of string at /share/apps/myourshaw/ensembl/ensembl-variation/modules/Bio/EnsEMBL/Variation/VariationFeature.pm line 1675, <GEN0> line 10050.</div><div>Use of uninitialized value in concatenation (.) or string at /share/apps/myourshaw/ensembl/ensembl-variation/modules/Bio/EnsEMBL/Variation/VariationFeature.pm line 1675, <GEN0> line 10050.</div>
<div><br></div><div>An example of a VCF input line is:</div><div>16<span style="white-space:pre-wrap"> </span>84497336<span style="white-space:pre-wrap"> </span>.<span style="white-space:pre-wrap"> </span>T<span style="white-space:pre-wrap"> </span>TAGTGGA<span style="white-space:pre-wrap"> </span>6710.07<span style="white-space:pre-wrap"> </span>InDel<span style="white-space:pre-wrap"> </span>AC=1;AF=0.50;AN=2;BaseQRankSum=-7.179;DP=159;FS=2.028;GC=55.61;HRun=0;HaplotypeScore=765.4756;IndelType=INS.NumRepetitions_1.EventLength_6.;MQ=153.37;MQ0=0;MQ0Fraction=0.0000;MQRankSum=5.013;Num454=0;NumOther=0;NumSLX=159;NumSOLiD=0;QD=42.20;ReadPosRankSum=-0.390;SB=-3325.82;SBD=1.32<span style="white-space:pre-wrap"> </span>GT:AD:DP:GQ:PL<span style="white-space:pre-wrap"> </span>0/1:112,47:159:99:6710,0,4955</div>
<div><br></div><div>The code in VariationFeature.pm that throws the error is:</div><div><div><span style="white-space:pre-wrap"> </span> $hgvs_notation->{'hgvs'} .= substr($hgvs_notation->{'ref'},0,3) . $hgvs_notation->{'start'} . '_' . substr($hgvs_notation->{'ref'},3,3) . $hgvs_notation->{'end'} . $hgvs_notation->{'type'} . $hgvs_notation->{'alt’};</div>
</div><div><br></div><div>In this example, $hgvs_notation->{'ref’} is ‘X’.</div><div><br></div><div>So substr($hgvs_notation->{'ref'},3,3) emits a warning and returns undef.</div><div><br></div><div>Apparently this situation arises because the termination codon is being represented as ‘X’ instead of the 3-letter ‘Ter’</div>
<div><div><span style="white-space:pre-wrap"> </span># Replace termination codon code 'Ter' with the HGVS-preferred 'X'</div><div><span style="white-space:pre-wrap"> </span>$hgvs_notation->{'alt'} =~ s/Ter|\*/X/i;</div>
<div><span style="white-space:pre-wrap"> </span>$hgvs_notation->{'ref'} =~ s/Ter|\*/X/i;</div></div><div><br></div><div>Perhaps this is merely a case of an annoying warning the needs to be cleaned up. Possibly, also, something may end up missing in the HGVSp string. In my example, this string comes out as ENSP00000393378.2:p.X796_[?]797insTrpLysextX3 where nothing is at the position indicated by [?].</div>
<div><br></div><div>This example raises another question.</div><div><br></div><div>Is it correct to append “extX3” to the HGVSp string if what is going on here is an insert after the stop codon rather than a lost stop?</div>
<div><div style="word-wrap:break-word;font-family:Helvetica;font-size:12px"><p class="MsoNormal" style="font-family:'Lucida Grande';font-size:10px"><font face="'Devanagari MT'" size="7"><span style="font-size:27px"><font size="5"><span style="font-size:18px">ॐ</span></font></span></font></p>
<p></p><p style="margin-top:0px;margin-right:0px;margin-bottom:6px;margin-left:0px;line-height:19px"><span style="font-family:'Lucida Grande';font-size:10px">Michael Yourshaw</span></p><div style="margin-top:0px;margin-right:0px;margin-bottom:0px;margin-left:0px">
<span style="letter-spacing:0px">UCLA Geffen School of Medicine</span></div><div style="margin-top:0px;margin-right:0px;margin-bottom:0px;margin-left:0px"><span style="letter-spacing:0px">Department of Human Genetics, Nelson Lab</span></div>
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