Gene variance of unknown significance

[djtippietoes]

Maybe you guys can explain this better to me than the genetic counselor. DS (3) had some genetic testing done and it was determined that there was a variance of unknown significance on a gene that has something to do with the pituitary gland. The genetic counselor said that since it's of unknown significance, it's not pathogenic, meaning that there's nothing wrong there.

This is confusing to me. Wouldn't unknown significance mean they don't know if it's pathogenic or not? I've spoken to the counselor several times about it and I'm still really unclear. The test he had was for genetic causes of short stature, so it would make sense that something could be going on with this pituitary gland, but the genetic counselor kept assuring me there wasn't.

So my question is - has anyone gotten this diagnosis about any gene (if you can call it a diagnosis) and the variance has actually amounted to the cause of an issue?

[luvboston]

We got it and the counselor is wrong get a new one. It means they don't have information on it yet or that only a ridiculously small # of people have that variant. In my kid his is only in .002% of the population but his doctor did a lot of reasearch and found 1 other person in the world they had written a paper on and got the info for us. However they will do more testing to figure out if it matters.
Do u see an actual geneticist or just a counselor?

[djtippietoes]

Feb 9, 2017 9:02:36 GMT -5 luvboston said:

We got it and the counselor is wrong get a new one. It means they don't have information on it yet or that only a ridiculously small # of people have that variant. In my kid his is only in .002% of the population but his doctor did a lot of reasearch and found 1 other person in the world they had written a paper on and got the info for us. However they will do more testing to figure out if it matters.
Do u see an actual geneticist or just a counselor?

You mean get a new counselor? The woman we spoke with was a  counselor, but she's been in the field for over 35 years and is highly regarded. She orders tests as though she was an actual geneticist, which is sort of odd, I guess and I'm assuming she has some sort of actual geneticist actually order them. She didn't seem to think it mattered, which was odd to me. 

I'm sure it's not the same gene as your son, but just in case, it was the GLI2 gene.

[Deleted]

She may not be wrong, but not explaining it well. Also, just because they are highly regarded in the field etc does not mean that it isn't still good to seek out a second opinion especially if you have questions that she is not answering to your satisfaction.

You can also check with the your regular pediatrician what they think, since I think they would be treating it anyway instead of the counselor. Like the counselor is just doing the testing and explanation but the pediatrician or your other doctors would interpret it into treatment if necessary.

[chickypoo2468]

From what I understand is the variant of unknown significance just means they don't know if it's normally pathogenic or not and research is still being done.

We had 3 of these and they looked into the disorders each one causes but didn't think any fit. A lot had similar traits, but not close enough. My other son gave a spit sample so that they can compare his DNA to O's to add to their knowledge on one of the genes.

It's not cut and dry. It's not like one variant always means one syndrome.

Our genetic counselor said they have a computer that they plug all this stuff into and the computer says if the variant would cause the issues.

New gene mutations are being added all the time, so what is of unknown significance now can have a name in a few years.

[chickypoo2468]

Feb 9, 2017 9:37:31 GMT -5 djtippietoes said:

Feb 9, 2017 9:02:36 GMT -5 luvboston said:

We got it and the counselor is wrong get a new one. It means they don't have information on it yet or that only a ridiculously small # of people have that variant. In my kid his is only in .002% of the population but his doctor did a lot of reasearch and found 1 other person in the world they had written a paper on and got the info for us. However they will do more testing to figure out if it matters.
Do u see an actual geneticist or just a counselor?

You mean get a new counselor? The woman we spoke with was a  counselor, but she's been in the field for over 35 years and is highly regarded. She orders tests as though she was an actual geneticist, which is sort of odd, I guess and I'm assuming she has some sort of actual geneticist actually order them. She didn't seem to think it mattered, which was odd to me. 

I'm sure it's not the same gene as your son, but just in case, it was the GLI2 gene.

Our genetic counselor ordered tests. It was an issue when I went to an outside lab and she wasn't an actual doctor, she was an RN and something else. I guess the she just orders them under the actual geneticist, even though his name wasn't in the order anywhere.

[luvboston]

djtippietoes yes get a new counselor or please see an actual geneticist. Who is the head of your team of doctors that person would take this mutation into account and figure out whether a condition fits as part of the picture. Also you want someone on your team to know about this so they keep theirs ears open if someone figures out a condition is related to this variant.
We don't have the same gene variant as you unfortunately.

[djtippietoes]

Does the unknown significance ever end up being no significance?

[luvboston]

I looked up the gene it's associated with many things including cancer. Obviously I don't have your variant in front of me but I again suggest a second opinion.

[djtippietoes]

luvboston, my gene is associated with issues in the pituitary gland and in more severe cases, the hemispheres of the brain. The reason the counselor didn't seem to think it was an issue was because he also had a growth hormone test which came back normal. So I guess her thought is that his pituitary gland is doing its job. Maybe a question for an endo really.

[chickypoo2468]

Feb 10, 2017 6:09:07 GMT -5 djtippietoes said:

luvboston, my gene is associated with issues in the pituitary gland and in more severe cases, the hemispheres of the brain. The reason the counselor didn't seem to think it was an issue was because he also had a growth hormone test which came back normal. So I guess her thought is that his pituitary gland is doing its job. Maybe a question for an endo really.

This makes sense. Sounds like that test rules it out.

For ours they did a cholesterol test. Low cholesterol confirms.

[djtippietoes]

chickypoo2468, We had that test done too. Hydrocholesterol 9 or something like that?

[chickypoo2468]

Feb 10, 2017 10:29:27 GMT -5 djtippietoes said:

chickypoo2468, We had that test done too. Hydrocholesterol 9 or something like that?

One was 7-dehydrocholesterol, Smith-Lemli-Opitz screen is listed as the test name.
The other is a lipid panel, Cholesterol SerPl QN

[djtippietoes]

chickypoo2468, yes, ours was for smith-lemli-optiz as well. My son does not have that. Does yours?

[chickypoo2468]

Feb 10, 2017 16:03:41 GMT -5 djtippietoes said:

chickypoo2468, yes, ours was for smith-lemli-optiz as well. My son does not have that. Does yours?

Nope. Back to the drawing board

[cribs4life]

I am way late to this but have you talked to your geneticist about this? We have sought a second opinion for my son's gentic disorder. His is pku so really well know but it was good to meet with a second person to go over everything and confirm our treatment plan

[djtippietoes]

Feb 16, 2017 20:11:39 GMT -5 cribs4life said:

I am way late to this but have you talked to your geneticist about this? We have sought a second opinion for my son's gentic disorder. His is pku so really well know but it was good to meet with a second person to go over everything and confirm our treatment plan

We are doing a second part of that test, where they see if there are deletions or duplications on said genes. The first part was sequencing. (I'm not entirely sure what sequencing means tbh!)

Interesting that your son has PKU because one of my best friends and her husband found out they are both carriers for that. I had not heard of it before.

[cribs4life]

Feb 17, 2017 7:28:00 GMT -5 djtippietoes said:

Feb 16, 2017 20:11:39 GMT -5 cribs4life said:

I am way late to this but have you talked to your geneticist about this? We have sought a second opinion for my son's gentic disorder. His is pku so really well know but it was good to meet with a second person to go over everything and confirm our treatment plan

We are doing a second part of that test, where they see if there are deletions or duplications on said genes. The first part was sequencing. (I'm not entirely sure what sequencing means tbh!)

Interesting that your son has PKU because one of my best friends and her husband found out they are both carriers for that. I hamd not heard of it before.

This is nosey but how come they did testing? You only really test if one of your relatives have it. Feel free to give her my name on here if she needs someone to talk to about it



I would ask the gentic counselor to clarify what she means by sequencing bc to find that muttation I would have thought they would they would have already looked for deletions or duplications.

[djtippietoes]

cribs4life, they are both jewish and it's part of the panel of jewish tests that you can do.

[cribs4life]

That's really odd because PKU is really low in the jewish population. It is really big in Irish populations.

Do they live in Israel? I know the government pays for or covers genetic testing. I wish we had something in the US like that. I have friends who haven't even gotten the testing done for PKU bc even though their kid has PKU the insurance won't test to specifically see what mutation it is.

[djtippietoes]

Feb 17, 2017 16:55:56 GMT -5 cribs4life said:

That's really odd because PKU is really low in the jewish population. It is really big in Irish populations.

Do they live in Israel? I know the government pays for or covers genetic testing. I wish we had something in the US like that. I have friends who haven't even gotten the testing done for PKU bc even though their kid has PKU the insurance won't test to specifically see what mutation it is.

No, they live in the US. 

[chickypoo2468]

Feb 17, 2017 8:05:41 GMT -5 cribs4life said:

Feb 17, 2017 7:28:00 GMT -5 djtippietoes said:

We are doing a second part of that test, where they see if there are deletions or duplications on said genes. The first part was sequencing. (I'm not entirely sure what sequencing means tbh!)

Interesting that your son has PKU because one of my best friends and her husband found out they are both carriers for that. I hamd not heard of it before.

This is nosey but how come they did testing? You only really test if one of your relatives have it. Feel free to give her my name on here if she needs someone to talk to about it



I would ask the gentic counselor to clarify what she means by sequencing bc to find that muttation I would have thought they would they would have already looked for deletions or duplications.

O has a pathogenic variant- for SLOS- but it was only on one copy so he should just be a carrier.
Sometimes there is a third copy and the variant can be on that one as well, but the initial test only looked for 2 and found 2 then stopped there. So further testing would be required to see if there is another one.
Could that be what they meant? Like the idea, not that specific gene.

[chickypoo2468]

Do you know the name of the panel?

[djtippietoes]

chickypoo2468 , it's this: www.egl-eurofins.com/tests/?testid=XM010

I'm seriously so confused! We're doing the duplication/deletion portion of it now, so I'm going to just wait until we get those results.

A also got something back (I didn't mention this before) that said he had a pathogenic variant on a gene that causes progeria. But same as your O, he was just a carrier for it, so I didn't really give it much thought.

[chickypoo2468]

Feb 18, 2017 14:03:52 GMT -5 djtippietoes said:

chickypoo2468 , it's this: www.egl-eurofins.com/tests/?testid=XM010

I'm seriously so confused! We're doing the duplication/deletion portion of it now, so I'm going to just wait until we get those results.

A also got something back (I didn't mention this before) that said he had a pathogenic variant on a gene that causes progeria. But same as your O, he was just a carrier for it, so I didn't really give it much thought.

Oh, it says the sequencing part doesn't detect large deletions or duplications, so maybe that's why?
I swear, it seems like it would be more cost effective to just doThe WES at the beginning instead of the other 8 million tests they do first. But I guess the ones who get results on the first try balance it out.

[djtippietoes]

chickypoo2468, YES! I feel like I've spent so much on these tests that I could have already paid for whole exome sequencing (which is what they're suggesting next if the duplication/deletion part of the short stature panel comes back normal.)

[djtippietoes]

So we got back the second part of that test which is testing for duplications and deletions on those particular genes and it came back normal. So basically they told me to wait another year and go back to the geneticist then. I know I should be glad that nothing was wrong on the second test (and I am!) but it's still more of the same - something is wrong with your kid, but we don't know what.

[chickypoo2468]

Mar 8, 2017 15:20:45 GMT -5 djtippietoes said:

So we got back the second part of that test which is testing for duplications and deletions on those particular genes and it came back normal. So basically they told me to wait another year and go back to the geneticist then. I know I should be glad that nothing was wrong on the second test (and I am!) but it's still more of the same - something is wrong with your kid, but we don't know what.

Wait a year for what exactly? Can you just push for WES?
There's a study that's doing WGS. Someone posted it in a fb group, let me go look for it. I started to apply but I don't know now.

[chickypoo2468]

www.raregenomics.org/ihope/

[djtippietoes]

Mar 8, 2017 22:17:54 GMT -5 chickypoo2468 said:

www.raregenomics.org/ihope/

Thanks.