Answers.Body: <p>It's the position in the protein. <code>p.Arg452Pro</code> means that there is a variant that changes an <strong>Arg</strong>inine residue at position 452 of the protein into a <strong>Pro</strong>line. </p>
  
  <p>And yes, it is absolutely possible to have the same HGVS p. notation on the same gene but on different transcripts. More than possible, it is quite common. Your particular example isn't actually a real variant since that position on chromosome 4 is intronic in both hg19 and hg38, but <a href="https://varso.me/oi" rel="nofollow noreferrer">TP53:p.R175L</a><sup>1</sup> is a real example of what you describe:</p>
  
  <p><a href="https://i.sstatic.net/IBHKo.png" rel="nofollow noreferrer"><img src="https://i.sstatic.net/IBHKo.png" alt="screenshot of varsome.com page for TP53:p.R175L"></a></p>
  
  <p>As you can see in the image or by visiting <a href="https://varso.me/oi" rel="nofollow noreferrer">the link</a>, this variant on TP53 has the same HGVS p. notation on 6 transcripts. It also has a different p. notation on two more transcripts that are not shown in the image as well as no p. notation for a few other transcripts in which it doesn't affect the protein product.</p>
  
  <hr>
  
  <p><sup>1</sup><sub>Disclaimer: The link goes to <a href="https://varsome.com" rel="nofollow noreferrer">https://varsome.com</a>, a free human variant search engine that is developed by the company I work for. </sub></p>
  
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Answers.Text: I actually gave a random position lol... but thanks for the explanation. Then, I have another question, what does the protein position 452 mean? Is it the number of the protein for that gene on the exons for that specific transcript ? it's not the genomic position, right ? For example, if we have a different transcript, with the position 453, can I say that the previous amino acid is 452 Arginine ?
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Answers.Text: @Law it's the position in the _protein_ that is produced when the transcript is translated. The number refers to the protein sequence, not the genomic sequence and not the transcript sequence. The 1st amino acid is at position 1, the second at position 2 etc. Your putative variant would be at position 452, it would affect the four hundredth and fifty second amino acid. Whether that is the same for another transcript will depend on what that transcript codes for.
Answers.UserDisplayName: terdon
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Answers.Text: Do you know if clinical diagnostics are transcript-dependent, or would the same protein change on different transcripts be considered equivalent for clinical purposes?
Answers.UserDisplayName: Brady Gilg
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Answers.Text: @BradyGilg that depends entirely on the transcript and protein in question. Do both proteins have the same function? Are they expressed in the same tissue? This isn't a simple question. You might want to post a new question instead.
Answers.UserDisplayName: terdon
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Answers.Text: What terdon has answered is right. For more details you can visit the official HGVS recommendations [here](https://varnomen.hgvs.org/)
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Body: <p>Let's take the example <code>p.Arg452Pro</code> that I got from an annotated VCF file that contains an <code>HGVSp</code> column.</p>
  
  <p>What does <code>452</code> mean in this case ? </p>
  
  <p>Theoretically, is it possible to have the same <code>HGVSp</code> on the same gene but on a different transcript level ?</p>
  
  <p>For example:</p>
  
  <pre><code>Chromosome      Position        Ensembl_Gene        Ensembl_transcript      HGVSp
  4               4613173         ENSG00052342        ENST00141456            p.Arg452Pro
  4               4613176         ENSG00052342        ENST00141458            p.Arg452Pro
  </code></pre>
  
  <p>Thank you in advance.</p>
  
Comments.ContentLicense: CC BY-SA 4.0
Comments.CreationDate: 2020-05-04T09:27:15.407Z
Comments.Text: the 452 amino acid of the protein?
Comments.UserDisplayName: StupidWolf
Tags: <vcf><sequence-annotation>
Title: What does the number mean in an HGVSp annotation?
ThreadText: # What does the number mean in an HGVSp annotation?
  
  (Asked by: username_0 on 2020-05-04)
  
  Let's take the example `p.Arg452Pro` that I got from an annotated VCF file that contains an `HGVSp` column.
  
  What does `452` mean in this case ?
  
  Theoretically, is it possible to have the same `HGVSp` on the same gene but on a different transcript level ?
  
  For example:
  
  ```
  Chromosome      Position        Ensembl_Gene        Ensembl_transcript      HGVSp
  4               4613173         ENSG00052342        ENST00141456            p.Arg452Pro
  4               4613176         ENSG00052342        ENST00141458            p.Arg452Pro
  
  ```
  
  Thank you in advance.
  
  **Tags:** vcf, sequence-annotation
  
  > **Comments:**
  > **username_1**: the 452 amino acid of the protein?  
  
  ---
  
  ## 1 answers
  
  ### Answer by username_2 on 2020-05-04. Score: 4 | Accepted answer
  
  It's the position in the protein. `p.Arg452Pro` means that there is a variant that changes an **Arg**inine residue at position 452 of the protein into a **Pro**line.
  
  And yes, it is absolutely possible to have the same HGVS p. notation on the same gene but on different transcripts. More than possible, it is quite common. Your particular example isn't actually a real variant since that position on chromosome 4 is intronic in both hg19 and hg38, but [TP53:p.R175L](https://varso.me/oi)1 is a real example of what you describe:
  
  [![screenshot of varsome.com page for TP53:p.R175L](https://i.sstatic.net/IBHKo.png)](https://i.sstatic.net/IBHKo.png)
  
  As you can see in the image or by visiting [the link](https://varso.me/oi), this variant on TP53 has the same HGVS p. notation on 6 transcripts. It also has a different p. notation on two more transcripts that are not shown in the image as well as no p. notation for a few other transcripts in which it doesn't affect the protein product.
  
  ---
  
  1Disclaimer: The link goes to <https://varsome.com>, a free human variant search engine that is developed by the company I work for.
  
  > **Comments:**
  > **username_0**: I actually gave a random position lol... but thanks for the explanation. Then, I have another question, what does the protein position 452 mean? Is it the number of the protein for that gene on the exons for that specific transcript ? it's not the genomic position, right ? For example, if we have a different transcript, with the position 453, can I say that the previous amino acid is 452 Arginine ?  
  > **username_2**: @Law it's the position in the _protein_ that is produced when the transcript is translated. The number refers to the protein sequence, not the genomic sequence and not the transcript sequence. The 1st amino acid is at position 1, the second at position 2 etc. Your putative variant would be at position 452, it would affect the four hundredth and fifty second amino acid. Whether that is the same for another transcript will depend on what that transcript codes for.  
  > **username_3**: Do you know if clinical diagnostics are transcript-dependent, or would the same protein change on different transcripts be considered equivalent for clinical purposes?  
  > **username_2**: @username_3 that depends entirely on the transcript and protein in question. Do both proteins have the same function? Are they expressed in the same tissue? This isn't a simple question. You might want to post a new question instead.  
  > **username_4**: What username_2 has answered is right. For more details you can visit the official HGVS recommendations [here](https://varnomen.hgvs.org/)  
  
  ---
  
  