Wrong amino acid substitution information

[Shawn Phillips]

Hello, 

I am an undergraduate student in Australia who used UCSC for the first time last week. We have been tasked to do some research on mutations within a chosen keratin gene and have chosen Keratin I (Krt1). The task requires us to compile some information from OMIM, UCSC and COSMIC to describe the gene as well as a disease state.

Anyway, using OMIM it is simple enough to find information on chromosome location, function etc and I chose to look at the autosomal dominant disorder Epidermomylotic hyperkeratosis 1. In OMIM, it says my disorder is caused by a SNP resulting in E310Q missense mutation and references the paper I have linked below. However, when I click on the NCBI and UCSC hyperlinks for the mutation it suddenly says that the mutation is E311Q missense. So I want to know, which source do I trust? OMIM + research paper or NCBI + UCSC? Furthmore, NCBI lists the source for the SNP as the research paper below which states its E310Q missense not E311Q. Is it possible that the UCSC and NCBI database has been updated on information not linked? What info should I believe?

Sorry for the ramble, and thank you for reading.

https://www.ncbi.nlm.nih.gov/snp/?term=rs137853224 

https://www.ncbi.nlm.nih.gov/snp/rs137853224#publications

Rothnagel, J. A., et al. “Mutations in the Rod Domains of Keratins 1 and 10 in Epidermolytic Hyperkeratosis.” Science, vol. 257, no. 5073, 1992, pp. 1128–30. JSTOR, http://www.jstor.org/stable/2879848. Accessed 24 May 2025.

[Clay Fischer]

Hi Shawn,

Thank you for your question about OMIM variation across the UCSC Genome Browser, NCBI, a publication and OMIM itself.

Our OMIM data is updated weekly in automatic process directly from OMIM, it was last updated on June 11, 2025.

Unfortunately, we cannot advise on scientific interpretation, only assist with UCSC Genome Browser tools and data. We advise you to contact the operators of the OMIM website about their linking of information to epidermolytic hyperkeratosis 1.

I hope this is helpful. If you have any further questions, please reply to gen...@soe.ucsc.edu. All messages sent to that address are archived on a publicly accessible Google Groups forum. If your question includes sensitive data, you may send it instead to genom...@soe.ucsc.edu.

Thanks,

--
Clay
UCSC Genomics Institute

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[Robert Kuhn]

Dear Shawn,

The paper you cite is from 1992, in the pre-genomic era.  Many proteins have the initial Methionine removed

after translation.

In the early days, many proteins were numbered without the Met.  That may account for the off-by-one situation

you observe.  As OMIM is reporting on the 1992 paper, it echoes the nomenclature from the paper.  The rsID

you cite, rs137853224, maps to a nucleotide in E311.

There is an early variant the hemoglobin gene from that period that is famous for this situation.  It is easy to see

at the 5'-end of the HBB gene, where the start codon is nearby.

In OMIM, you see 

   http://www.omim.org/entry/141900#0451 

   Hemoglobin Tyne

and if you read the entry, it refers to "codon 5."  In the Browser, you see that it is the proline #6 if you count

the MET, and would be #5 in the literature of the time (1994).  See it highlighted in the Browser:

    https://genome.ucsc.edu/s/Example/hg38_HBB_AA6

best regards,

    --b0b kuhn

Robert Kuhn, PhD

Associate Director UCSC Genome Browser (retired)

dba Robert Kuhn Consulting

To view this discussion visit https://groups.google.com/a/soe.ucsc.edu/d/msgid/genome/CAEiWAOSk6GoOVfvgSPf8YzoFwL0CPw7R0p2o%3DT4Y6MQ_a5NadQ%40mail.gmail.com.