# What does the number mean in an HGVSp annotation?

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


• the 452 amino acid of the protein? – StupidWolf May 4 at 9:27

It's the position in the protein. p.Arg452Pro means that there is a variant that changes an Arginine residue at position 452 of the protein into a Proline.

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.R175L1 is a real example of what you describe:

As you can see in the image or by visiting the link, 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.

• 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 ? – Law May 4 at 10:38
• @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. – terdon May 4 at 10:47
• Do you know if clinical diagnostics are transcript-dependent, or would the same protein change on different transcripts be considered equivalent for clinical purposes? – Brady Gilg May 4 at 19:19
• @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. – terdon May 4 at 20:20