Anyone with Exon 12 mutation out there?

[gvibes]

Hi Everyone, I was diagnosed a year and a half ago with polycythemia vera with a negative v617f mutation and a positive Exon 12 mutation. The literature says that about 95% of the p-vera cases are positive for v617f while 3% have one of many Exon 12 mutations. The disease presents itself a little differently for v617f versus Exon 12. I guess because the genetic testing for Exon 12 is more complicated and expensive, its possible that people who are v617f negative but not further tested may have Exon 12 mutations.

I am wondering if anyone else has been identified with Exon 12 (or perhaps v617f negative) and what have been their experiences.

Appreciate it

[WeylandYutani]

Hello gvibes,

I have been tested Exon12 positive in January 2021; since July 2021 I'm taking Besremi with quite good results. What I experienced so far is, that my white blood cell count is not elevated - which sometimes causes issues with the Interferon dosage. I also was able to get a document from a french group of scientists who compared V617F with Exon 12 with respect to overall survival etc (spoiler: there is not a lot of difference).

Please let me know what you are interested in; we can also get in touch to share information etc.

Best regards

[Wyebird]

Interesting I know little about exon mutations. Does that mean you won’t have Jak2 or Calr Mutation?

[gvibes in reply to Wyebird]

Exon 12 is still Jak 2. V617f is exon 14 but somehow the two mutations are close together physically as the genetic material wraps around each other. There is a diagram that I saw ina paper that I will try to find and post. I have never been told that I have a CALR mutation. I’m outside my understanding here a bit. Others know much more.

[Wyebird in reply to gvibes]

Thanks, my understanding is you ar jak or Calr . I’m Calr

[EPguy in reply to gvibes]

I don't know that much either, but here is a bit on it as I understand. Mostly it describes the location of the defect in the Jak2 gene. CALR and MPL are different genes and so very different defect locations. But all these types are connected since they operate together in our marrow (mal)functions.

I've heard the same that Exon 12 is a more costly inspection, so they look for regular exon 14 first.

V617F (exon 14) <<replaces the protein building block (amino acid) valine with the amino acid phenylalanine at position 617 in the protein. ... A small number of affected individuals have a somatic mutation in another part of the JAK2 gene known as exon 12>>

medlineplus.gov/genetics/ge...

Other members here likely know more or better details.

[gvibes]

Let me change “a bit” to “a lot”.

[gvibes]

Thanks EP Guy.

Heres a depiction (Linda Scott 2011) showing genetic region

exon 12/v617f region