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Note: this question has also been asked on BioStars

I am getting peptides using biomaRt library in R for the gene 'BRCA1'. 27 different aminoacid sequences are returned, and 12 of those have an asterisk (*) in the end, while 15 do not. What does that mean? I know that asterisk is used to indicate stop codon. So, does that mean the peptides without an asterisk do not have a stop codon? Is that possible at all? Are all of those valid peptides or not?

Below is the R code I used:

library(biomaRt);
mart = useMart('ensembl', dataset='hsapiens_gene_ensembl');
seq = getSequence(id='BRCA1', type='hgnc_symbol', seqType='peptide', mart = mart);

MDLSALRVEEVQNVINAMQKILECPICLELIKEPVSTKCDHIFCKVLLCCPSWSTVVRS* is an example sequence with an asterisk in the end. MDLSALRVEEVQNVINAMQKILECPICLELIKEPVSTKCDHIFCKSLQESTRFSQLVEEL‌​LKIICAFQLDTGLEYANSYN‌​FAKKENNSPEHLKDEVSI is an example without an asterisk.

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If it's 3' incomplete that means the evidence used to create it was a fragment. Here's the evidence used to construct BRCA1-214 ENST00000477152.5, a 3' incomplete.

You can see that there's a full length cDNA from EMBL, AK307553.1, which was used to create this model.

The sequence was mapped against the genome sequence to create the transcript model. When searching for the translation, it was found that the open reading frame was started, but there was no stop codon. This suggests that the cDNA AK307553.1 is actually a fragment, that the mRNA was broken or cleaved before it was reverse-transcribed sequenced. We display it in Ensembl in the hope that this will lead someone to identify the full length transcript that it represents.

Many people choose not to work with these incomplete transcripts. You can do this by filtering by Gencode Basic in biomaRt.

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If you look at the original data at Ensembl you'll notice that most of these are labeled "CDS 3' incomplete" and have a TSL (transcript support level) of 1, which is as low as it goes. It seems likely that that is simply an incomplete annotation. I'm not surprised that there are a bunch of these for BRCA1, since there was a long time when there were a LOT of legal issues surrounding working on it.

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    $\begingroup$ @DevonRyan TSL1 is the most reliable, TSL5 is the least. Also, OP, there are some times of day when you might get an answer instantly, but mostly I would assume a full working day is a reasonable amount of time to wait before impatiently crossposting everywhere. You don't know where in the world the one or two experts who can answer your question are, and what time they'll get onto the web. $\endgroup$ Aug 15 '17 at 8:57
  • $\begingroup$ @EmilyPerry Gah! Thanks for letting me know about my TSL mistake. How the heck did an annotated "incomplete" transcript get a TSL of 1? $\endgroup$
    – Devon Ryan
    Aug 15 '17 at 9:10
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    $\begingroup$ Still won't let me comment. Devon, TSL and incomplete are independent. It's TSL1 because there is at least one non-suspect piece of evidence that covers the whole thing. If all we've got is evidence of a fragment, then that's all we've got, but the evidence of that fragment is strong. $\endgroup$ Aug 15 '17 at 10:58
  • $\begingroup$ @EmilyPerry Sorry, that's an annoying stackexchange thing, you need 50 rep to comment. Anyway, thanks for clarifying that TSL and "3' incomplete" are independent annotations! $\endgroup$
    – Devon Ryan
    Aug 15 '17 at 11:07
  • $\begingroup$ @EmilyPerry I am not a bioinformatician or a biologist, so I don't really understand what a "non-suspect piece of evidence that covers the whole thing" means. Does it mean that this sequence with no asterisk in the end was found as a protein synthesized by the gene? Probably not since there is no stop codon, right? Or does it mean that an mRNA that matches this peptide sequence was measured? The mRNA without a stop codon would be degraded, though.. Sorry if this is a dumb question, but I'd really appreciate some clarification on that. $\endgroup$
    – user5054
    Aug 16 '17 at 0:33

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