Today I set out to compile an exhaustive list of rare variants in PRNP which have been reported to be pathogenic. I am posting this list here as a reference. Here are some disclaimers:
- This does not constitute an endorsement that each of these variants is indeed associated with prion disease risk - some may actually be benign. This is just a review of what has been reported in the literature.
- The “see also” column is far from exhaustive. Many of these variants have been discussed in tens of publications.
- I compiled this list by reading two reviews [Kong 2004, Beck 2010] and OMIM #176640 and by searching PubMed for new reports since 2010. After initial publication of this post, Simon Mead pointed out a few variants I had missed. Co-authors of [Minikel 2016] later pointed out further edits. As of the last updated date below, I think this is complete but if you know of something I missed, please leave a comment below.
- I excluded any variants known to have an allele frequency >0.5% in at least one continental population, including 1-OPRD [Palmer 1993], and G54S, M129V, G142S, N171S, and E219K.
Last updated 2018-07-11, now contains 69 variants.
* Variant is suggested to be a risk factor.