BRCA1 -- "variant of unknown significance"

Andrea, several percent of all tests come back with "variants of unknown significance". It isn't uncommon at all, unfortunately. These variants aren't studied throughly enough to tell with absolute clarity if they are (or aren't) dangerous. Over time, more info trickles in and the "classification" of the variants is updated. Most end up classified as normal benign variation. But some become classified as real dangerous mutations.

 Until this point in time is reached, the usual rule of thumb is to disregard the "unkown" variants. Not to use them for any medical decisions. There is a catch, however. "Unknown significance" doesn't mean that nothing is known about a variant. There may already be some info suggesting that the variant is inconsequential (or maybe that it looks dangerous). Just not as much, or as thorough, data to convince everybody to change the "classification" at last.

 But sometimes even partial info can help you make a decision!

 Another catch. If "classification" is updated, then a lab would normally send an updated test report to the patient. But your sister isn't there to receive an update, and to pass the info on to you. Maybe there was an update already, you need to find out. Which variant was hers? Have you looked it up on the Internet? Have you asked the lab, or genetic counselors? Remember, you have to be specific. Each variant has its own unique trail of evidence.

 And lastly. Have you checked at FORCE forums? They have a whole forum for discussion of specific variants:

 http://www.facingourrisk.org/messageboard/viewforum.php?f=311

I was at the doctors yesterday because I had discovered 2 lumps on my left breast about 3 months ago.  i am 30 years old.  I was also tested for genetic testing yesterday and they told me it took 3 weeks to come back.  If I have the gene they are suggesting to get a double masectomy.  What do you think?  Also, I had biopsies done yesterday, adn was wondering how long it takes for test results to come back?

I see that this thread moved some distance off-track Andrea, anything new / important you found out today?

Uh oh, more knowledge and less clarity. It's a common thread with genetic testing where the docs speak in "probabilities" and the counselors have pros, cons, and maybe's for every choice you are supposed to make.

 But you story may be particularly confusing, Andrea. Let me try to put it straight ... if only I got it right.

So Karen had some "IVS" (intervening sequence) variant (outside of the "exons" which actually do all the coding for the protein), and the clinical significance of this change was "uncertain". Maybe it contributed to her cancer horror, but more likely it didn't have anything to do with it?

Then you got tested too. Also a complete test of the two genes, just the way she did. Even though her test didn't find any real mutations anywhere. That's sort of unusual for genetic counselors to recommend, to keep testing in a family where a high risk member didn't get a positive result. But there might be a reason to keep testing in some cases. For example if there is strong family history in both father's and mother's families (and therefore if they haven't found a mutation in one high-risk relative, they may still be a mutation in another branch of the family).

 You also got an uncertain result, and it was a different variant. Now you know far a fact that your variant had absolutely nothing to do with your sister's cancer. This much is clear and it should be encouraging.

 Did you make a note, what were the exact names of the two "uncertains"?

Hi Andrea, my daughter was diagnosied with breast cancer 2 years ago but insurance wouldnt pay for gene testing, i was just diagnosed with bc a few months ago and was neg for the gene but it did come back as 'VOUS'  so the lab acturally wanted to find out if my daughter had that too and they paid for it, which scared me, she did come back with the same as mine, so now with this information we dont know what to do with it, they say it is a mystery and they may find out what it is or they may never know, iam trying to reach my dads side of the family (who has a lot of cancer on his side) to see if any one tested pos for this as well. so i wouldnt worry to much because this all is still so new and it may help on down the line some where or it may not, i wish i didnt even have this info because it just me crazy so try not to even think about it, Sorry to hear about your sister karen you are in my prayers.

angel hugs

debbie

Debbie, when the variant is "uncertain", one of the best ways to find out if there is a cancer connection is to do a follow-up testing in the families.

 If you find the variant in healthy relatives, and not in the relatives with cancer, it sort of tells you that the variant has nothing to with cancer.

 But if you keep finding the variant together with cancer, then bit by bit, the proof of the danger grows with every new patient.

The labs understand it, and promote follow-up testing in the families with uncertain variants, even giving away free tests, in hope of clarifying the uncertainty once and for all. But at the same time, the lab must tell the patients not to use these test results for any clinical decision yet. So there is a catch, one can get a freebie, but it isn't really useful until some later time, until after the uncertainty is sorted out.

And as you may guess, not too many people accept these free offers ... and it takes even longer to gather the information to resolve the uncertainty.

Like in Andrea's story. 12 different families had "her" specific variant, but only two of them followed on with testing of relatives. And it begins to look like the variant is benign ... but the case is still too weak, more data is needed to nail the conclusion, and who knows when more families would respond? Actually there is a 3rd family where the variant also does not track with cancer, and it is Andrea's own family, right? Although the lab probably doesn't even know about it, because there hasn't been any formal connection between Karen's and Andrea's tests.

 In your own story, the variant did track with cancer. No reason to worry yet, because there is a 50% probability of it happening just by chance. But once more families, or more distant relatives, are added to the study, the case will become more clear. As always with uncertain variants, you got to be specific, there may be enough info out there already to blow away most of the "mist of uncertainty". And a reminder, there is a forum where all variants are discussed "on individual basis":

http://www.facingourrisk.org/messageboard/viewforum.php?f=311

Got my genetic results back and counselor indicated I had a variant of unknown significance with the BRCA2 gene. However, she indicated there are only 2 documented findings of this variant and at this point they both look benign so she doesn't feel this is a consideration and that we should use clinical diagnostics instead. A breath of good news is great! Praise God! Now just waiting on MRI results so we can decide on surgery direction...

Stay positive!