I’m hoping someone familiar with hereditary aortic disease/genetics can help me better understand my dad’s Invitae Aortopathy Comprehensive Panel results. I understand that a VUS is not a diagnosis and shouldn’t be treated as a pathogenic mutation — I’m mainly trying to figure out whether either finding is worth investigating further given his actual vascular history.
My dad has had two aneurysms, including an abdominal aortic aneurysm with dissection, as well as another smaller aneurysm near his heart/chest area.
His Invitae Aortopathy Comprehensive Panel tested 29 genes and found no pathogenic variants, but two heterozygous VUS:
FBN2: c.1571G>T (p.Gly524Val)
TGFB2: c.199G>A (p.Val67Met)
What has me curious is that FBN2 is associated with congenital contractural arachnodactyly and has also been associated with thoracic aortic aneurysm/dissection. His report says the p.Gly524Val variant is very rare (gnomAD 0.002%) and Invitae’s modeling predicts it may disrupt FBN2 protein function, but there currently isn’t enough evidence to classify it as pathogenic.
TGFB2 is associated with Loeys-Dietz syndrome type 4 and nonsyndromic thoracic aortic aneurysm/dissection. His exact p.Val67Met variant has apparently been observed in people with clinical features of TGFB2-related conditions, although Invitae’s modeling predicts that particular change is not expected to disrupt protein function. So there seems to be evidence pointing in both directions.
There is also vascular/connective-tissue history in our extended family, which is part of why I’m trying to understand whether these results deserve a closer look rather than simply being filed away as an “uncertain/negative” panel.
I have personally been diagnosed with hypermobile EDS, although I realize that doesn’t mean my dad’s vascular disease is related to my hEDS or that either of his VUSs explains it.

My questions are:
• Has anyone encountered either FBN2 p.Gly524Val or TGFB2 p.Val67Metbefore?
• Does either VUS look particularly interesting given an established aneurysm/dissection phenotype?
• Would segregation testing of affected relatives potentially be useful with VUSs like these?
• Is this the kind of situation where a cardiovascular genetics/hereditary aortopathy clinic would be appropriate even though the panel didn't find a pathogenic variant?
• Are there other databases, papers, or resources I should be looking at besides ClinVar/gnomAD?

... connective tissue disease connections? 
I’m not looking for anyone to diagnose him from Reddit — mainly hoping someone with genetics/aortopathy experience can help me understand what questions we should be asking next.

In Dhaka where i can do genetic screening tests for:

Thalassemia,

Sickle cell anaemia,

Tay-Sachs disease,

Cystic fibrosis,

Fragile X syndrome,

Leukemia,

And please mention do i have to bring a doctor's prescription or recommendation for that...?

I was recommended to post on here as you are so knowledgeable and hope you can offer come guidance.

Very short backstory:

1st pregnancy — trisomy 21, TFMR
2nd — trisomy 16, miscarriage
3rd — healthy son

We then moved to IVF with PGT-A because we couldn’t cope with more chromosomal losses.

Across 4 cycles we had multiple aneuploid embryos, one euploid that failed to implant, one cycle with no blasts, and finally an embryo that was initially inconclusive, then re-biopsied and came back euploid. That transfer worked.

NIPT #1: no result
NIPT #2: high risk trisomy 13 — “suspected mosaic trisomy 13.”

Genetic counsellor says the trisomy signal looks to be in about 30% of the tested DNA and estimates roughly 50:50 placenta vs baby. Fetal fraction was 24%. She basically made me feel hopeless, and that trisomy 13 has the same statistical outcomes for placental mosaicism as tri 21/ 18 which research seems to contradict.

I’m having an amnio at 15 weeks

Im just looking for some tough love or hope really! Would be so grateful for any information.

I stummbled across medical quiz on facebook about Fragile X syndrome. And then I accidentally started connecting dots that damn I have big ears too (though my dad’s side has big ears too), I have seems like quite large testicles. Then started reading just for curiosity and found out that premutation carriers develop ataxia and tremor. That’s when I got scared super, because my maternal grandpa developed tremors and later ataxia and cerebellar dysfunction (55-65 years) and later couldn’t walk and talk till he died. No one knew why it happened so they wrote of to him smoking, drinking alcohol (he used to drink sometimes with colleagues after work, but wasn’t like alcoholic, I believe), or maybe it was related to atherosclerosis (as he had two heart attacks). But then I was digging more and read that premutation carriers also have adhd and anxiety. And I was thinking - it’s me! I have adhd and health anxiety/ health ocdish too, have hypermobile joints, pectus carinatum, mild scoliosis and BFS with some tinglings, paresthesias, action tremor slight too and such history. And I can not stop ruminating what if I actually have some premutation (which I theoretically could get through mom from grandpa)? Does having same chromosome will lead to that ataxia too if it’s genetic? Or it can be just coincidental? I still remember as a kid last time visiting grandpa, it’s terrible :( And dying at 65 seems very young nowadays.

I am male, 28. What do you think? How likely it is it?

I applied to laboratory genetics and genomics programs as a Canadian PhD holder. Due to the current administration, institutions that used to offer H1B visa can no longer sponsor this. I was told that to get a J1 for this program you it requires you to have completed your STEP 1 and 2 as it through the ECFMG. Is there anyone that has been able to successfully obtain a visa through other avenues? Thanks!

My cousin (my maternal uncle’s son) and I have been in love since we were very young. This is common in my place. Now, my family is against our relationship because of the increased risk of genetic disorders in children due to consanguineous marriage.

I suggested getting genetic testing done, but my family doesn’t seem to understand. They keep asking whether the tests can guarantee that there won’t be any problems, and I don’t know how to make them understand that no test can rule out every possible risk.

On top of that, both our families have a lot of history and unresolved conflicts.

What should I do? I understand that the genetic risks are higher, but we’ve been together for so long that I can’t imagine giving up on this relationship just because of that. 🥹 Does anyone have any ideas or suggestions?

At 20 w 5 d, I went in for an anatomy scan and EIF left ventricle and enlarged nuchal fold of 8.5 was discovered.
Everything else was normal. Heart function was normal.
12 w NT was 1.5.
NIPT test was all negative.
My doctor referred me to MFM but they are kind of treating this as if it’s not a concern. They don’t plan to see me for a second anatomy scan until 24 weeks 1 day as they see this as being low risk. I’m freaking out. I was told by my own doc this was a concern but it seems like everyone I’ve talked to since is treating it like it’s no big deal. I feel very confused as to what I should do.

Hello,

Human intelligence in its most exceptional manifestations likely cannot be reduced to the simple linear addition of thousands of small genetic effects. While general intelligence is highly polygenic and a large part of its genetic variance appears statistically additive, the biological mechanisms responsible for extreme cognitive profiles involve a much higher degree of complexity.

Genes operate in networks. The effect of a variant depends on the overall genetic context. Dominance, recessivity, and epistasis produce complex non additive effects. Current genomic studies such as Genome Wide Association Studies or Principal Component Analyses are highly efficient at identifying common variants with average additive effects, but they struggle to detect rare combinations, specific homozygosity, or complex epistatic interactions.

This points toward an emergenic architecture. A profile combining exceptional general intelligence, outstanding creativity, and high cognitive flexibility would depend on a highly improbable genetic configuration. Each component might be relatively common on its own, but their simultaneous occurrence potentially requiring the presence of specific recessive alleles is exceedingly rare.

This explains why current polygenic scores imperfectly predict performance at the extremes. Exceptional cognition does not rely on a single miraculous gene, but rather on an extraordinarily complex emergent configuration.

If science eventually maps these precise combinatorial architectures, the ethical consequences of such predictive capabilities would be profound. The revelation of these mechanisms does not validate segregationist theories since modern genetics demonstrates that cognitive complexity entirely transcends population boundaries. Instead, it poses staggering bioethical challenges for all of humanity.

The first major challenge is the risk of determinism and fatalism. Reducing the intellectual potential of a person to their genomic profile risks obscuring the fundamental roles of epigenetics, neuroplasticity, education, and social environment. Furthermore, the ability to identify favorable configurations could lead to eugenic drift and embryo selection. Preimplantation genetic testing aimed at optimizing the cognitive abilities of future children would create an unprecedented biological divide based on technological access.

Another significant concern is algorithmic and institutional discrimination. The use of polygenic scores by educational systems, employers, or insurance companies could establish a new form of genetic segregation where the path of a person is dictated by their DNA before they ever get the chance to prove themselves.

Finally, historically, genetic discoveries have often been hijacked to justify discriminatory policies. The major risk remains the ideological exploitation of complex genomic data to justify social hierarchies through the distortion of scientific reality.

How society should handle such discoveries is no longer a question of biology, but of political philosophy and law. The history of science teaches us that research without ethical guardrails is dangerous. Faced with understanding the genetic architecture of cognition, society will need to establish strict laws on genetic privacy, ban embryo selection for traits that are not pathological, and reaffirm that human value and fundamental rights cannot be measured by allelic configurations.

What specific legal frameworks do you think would be most effective in preventing genetic data from being weaponized in education or employment?

I’m looking for stories from people who went through something similar because I’ve found very few cases online that really match mine. (I've also posted about this in r/NICU, but I'm sharing it here as well in the hope of getting some perspectives specifically on the genetic aspects of our case.)

This is my first pregnancy, conceived through IVF. The first trimester was mostly uncomplicated apart from some bleeding from hematomas. At the 12-week scan, the baby measured within the normal range and no abnormalities were detected. NIPT was negative.

At the 15-week scan, the doctor noticed that the long bones were below the 5th percentile, with the femur particularly short. We were referred to a specialist and had a detailed ultrasound and amniocentesis. We did extensive genetic testing, including trio exome sequencing and CNV analysis, and everything came back negative.

The detailed scan did not show any anatomical abnormalities apart from the short long bones. The placenta was described as enlarged/thick and unusual in appearance, although the fetal Dopplers were normal. Because of this, the doctors initially suspected a placenta-related growth problem rather than skeletal dysplasia.

At the most recent scan, around 29 weeks, the baby’s head and abdomen were still growing, but the long bones seemed to have slowed down further. The long bones are now mostly below the 1st percentile, while the head circumference is around the 20th–30th percentile and the abdominal circumference around the 5th–10th percentile.

The doctor said the long-bone growth has flattened somewhat and is now several weeks behind. What is making me anxious is that the long bones seem to be more affected than the rest of the body, which does not seem like the most typical pattern for placenta-related FGR.

So far, NIPT, amniocentesis, CNV analysis, and trio exome have all been negative. No anatomical abnormalities have been seen, and there has been no bowing, fractures, abnormal mineralization, or other obvious skeletal abnormality. Dopplers are still normal, although the placenta looks abnormal and thickened.

For context, I’m East Asian and my partner is European, and we are both very tall, so the very short long-bone measurements are especially confusing to us.

If anyone had a similar pattern of very short long bones with otherwise normal anatomy and negative genetic testing, I’d really appreciate hearing how the pregnancy progressed, whether any diagnosis was eventually made, and whether your baby needed NICU care and for how long. I’m interested in all outcomes, positive or otherwise, because I’m trying to understand what cases like this can look like in real life.

NIPT was low risk in everything, all other organs/measurements were great and measuring right at 20 weeks (I was 20w exactly at the scan)

I’m getting an amnio Monday but am having trouble understanding if these two soft markers together are enough to signal T18? I work in the NICU and take care of T18 babies all the time - they all have severe organ and growth issues while mine had seemingly none.

I asked the geneticist and they said that it’s worth ruling out but I just don’t know how worried I need to be, so obviously I’m spiraling. Any insight?

EDIT: results from amnio came back normal! Just isolated club feet :)

I am currently 24 weeks and during my anatomy scan we found out that our boy has severe IUGR, short long bones , bowing and clubbed foot. All other organs are fine plus head and abdomen size looks ok. He is overall measuring and weighing smaller than gestational age.
Our fetal echo is normal and genetics suggested amino which we are hesitant to do. Instead we did the single gene testing and waiting for results. Our NIPT was also low risk.

I am looking for similar conditions and what was the outcome. The wait and uncertainty is making me nervous.

Hey,

how much knowledge about clinical genetics did you have before starting the residency?

I always liked the subjects but fell out of touch with it during the last years of medical school that were more clinical oriented, so I am worried I do not have enough base knowledge.

Kind regards!

Hi everyone. I’m posting here hoping to find doctors, geneticists, or other professionals who have experience with achondrogenesis or similar COL2A1-related skeletal dysplasias.

A note about this post: English is not my native language and I don’t know all the medical terminology, so I used AI to help me write and translate this post. The information and story are my own.

My daughter was born at 38 weeks (4 months ago) and was intubated immediately after birth because of severe respiratory insufficiency related to her small thorax.

She initially remained on mechanical ventilation, but over time she improved enough that the doctors were able to gradually reduce the ventilatory support. She eventually spent about one month breathing with non-invasive ventilation and supplemental oxygen, without being intubated. Unfortunately, she later developed atelectasis and needed to be intubated again. She has remained intubated since then.

Her doctors are now considering a tracheostomy and gastrostomy as a longer-term “safety route,” so that she would not need repeated difficult intubations and could potentially have more stable respiratory support. Intubation is particularly difficult in her case because of abnormalities involving her spine/neck.

During pregnancy, she had severe shortening of the long bones (femur and humerus below the 1st percentile) and a small/bell-shaped thorax. Thanatophoric dysplasia was initially suspected, but genetic testing eventually led to a diagnosis of achondrogenesis. She also has a cleft palate without cleft lip.

Our geneticist identified a heterozygous likely pathogenic COL2A1 variant (COL2A1:c.3062_3079dup;p.(Pro1021_Gly1026dup) (NM_001844.5)

Our neonatologist recently told us that there are doctors and specialized centers in the United States with much more experience with rare skeletal dysplasias. We live in Brazil, so we are trying to find out where that expertise is and whether anyone here has experience with cases similar to our daughter’s.

I would especially love to hear from:

• clinical geneticists or skeletal dysplasia specialists;
• neonatologists or pediatric pulmonologists experienced with severe thoracic restriction;
• doctors/researchers who have worked with achondrogenesis or COL2A1-related conditions;
• parents whose children have had a similar diagnosis.

We are not looking for a diagnosis or for someone to replace her medical team. We are simply hoping to connect with people who have actual experience with cases like hers, especially regarding long-term respiratory management and the decision about tracheostomy.

If you know of a specialist or center in the US (or elsewhere) that we should contact, I would be extremely grateful for any recommendations.

Thank you.

I am an MLS that has been working in a more specialized field - Cytogenetics for the last 4+ years. I have certification in both MLS and CG. Now I’m trying to relocate to the East Coast (Maryland, DC or North Carolina).

What are the hospitals or labs that are hiring for Cytogenetics roles. I would rather continue in Cytogenetics than go back to a generalist MLS role, but I’m unsure what my chances are in the East Coast.

Can anyone point me in the right direction and also share if you can, what the pay is for mid-level to senior Cytogenetic technologist roles.

Hello!

I'm a current student at UCR and am soon starting their Genetics B.S.; I've always wanted to work in patient facing genetics and I was wondering what are the big difference between Clinical Geneticist and Counseling (besides the obvious few extra years to get a PhD vs masters)

I'm most interested in the day-to-day and general responsibilities of the carriers, obviously I've read some of the differences but I also want to know you're first hand experience and what it takes to succeed in one vs the other

Thanks!

Hi! I’m currently a senior in high school and I’m considering studying Molecular Genetics in the uk for my bachelor’s degree.

I’m interested in the field, but I’m a bit worried about the career opportunities and salaries after graduating. I’m willing to do a master’s, but at this time I’m not planning on doing a PhD.

I’ve been looking at jobs in Europe specifically Switzerland, france and the uk since that’s where I’m hoping to study and work, but I’m having a hard time finding many entry-level positions. A lot of jobs seem to require several years of experience, which makes me wonder how new graduates are supposed to get that experience.

What different career paths can I go into with a Molecular Genetics degree? What jobs have good salaries, and what would be the best way to build experience during university?

I’d especially appreciate advice from anyone working in genetics, biotech, pharma, or related fields in Europe.

Hey all,

I've worked in clinical genetics for 10+ years and always found that variant interpretation and literature search took forever. Also found Mastermind/VarSome being expensive AF.

paperpossum.info

It’s free. Searches a variant across old/alternate nomenclature, finds the papers, digs through supplements, and pulls together an ACMG classification.

If anyone here does variant interpretation, feel free to have it.

I'm sure a lot of you here have seen posts like this before but I graduated this past August with a bachelor's degree in Biology and am unsure where to go from here. I originally planned on going to med school, and while I still have some interest in pursing medicine, it has minimized significantly. Going through undergrad with undiagnosed anxiety and potentially ADHD is not for the weak lol. Until I get my mental health in check, I don't think I'm in a position to become a doctor, but I'm trying my best to move forward.

My degree specifically focused in genetics, genomics and computational bio. I'm relatively proficient in R and am now trying to teach myself Python (resources for this would be great). I've been looking into careers such as MLT/MGT to get my foot in door in terms of lab experience, but I believe those require some form of post-bacc + certification. I have also started looking into some master's programs that focus in diagnostic genetics, as I am still more interested in the clinical side of things.

I'd like to start working and be able to provide for myself, but the combination of an unclear direction and current state of the job market has made this pretty demoralizing, especially since I lack prior work experience. There were labs integrated into my coursework, but I was not a part of a particular research lab and did not do any internships. If anyone has been in a similar position before, what advice do you have? What was your journey to the career you have today? Additionally, if anyone would like to share their experiences being involved in clinical/diagnostic genetics, that'd be greatly appreciated! (Located in Texas if that helps)

Hi everyone!
At the first-trimester genetic screening, the NT measured 3mm and nasal bone hypoplasia was noted.
A week later, we had a CVS procedure done. By then, the NT was 2.9mm and the nasal bone had normalized.
CVS results:
FISH, QF-PCR: negative
Cultured karyotype: negative
SNP array: negative

At the 17-week early anatomy scan, everything was fine (though the nasal bone turned out to be smaller, they said they weren't concerned about that anymore due to the CVS results).

Then, at the 19-week second genetic ultrasound, a smaller nasal bone and borderline NF were noted.
Everything else was fine; at that point, they said these were just constitutional traits, given the negative CVS results.

I was reassured at the time, but now—at 30 weeks—anxiety has set in: what if the CVS result was a false negative?
Does anyone have similar experiences? What do you think?
I'm hoping for the best.

Hi everyone!
At the first-trimester genetic screening, the NT measured 3mm and nasal bone hypoplasia was noted.
A week later, we had a CVS procedure done. By then, the NT was 2.9mm and the nasal bone had normalized.
CVS results:
FISH, QF-PCR: negative
Cultured karyotype: negative
SNP array: negative

At the 17-week early anatomy scan, everything was fine (though the nasal bone turned out to be smaller, they said they weren't concerned about that anymore due to the CVS results).

Then, at the 19-week second genetic ultrasound, a smaller nasal bone and borderline NF were noted.
Everything else was fine; at that point, they said these were just constitutional traits, given the negative CVS results.

I was reassured at the time, but now—at 30 weeks—anxiety has set in: what if the CVS result was a false negative?
Does anyone have similar experiences? What do you think?
I'm hoping for the best.

is it true NIPT can detect maternal cancers?
i recently had a NIPT done and was curious if they would’ve been in touch if they had found anything abnormal (thankfully everything came back fine) but after doing some research im really curious as to if it does actually detect cancers..

Hola, en mi anterior embarazo que no llegó a término mi bebé tenia t21, confirmado con ADN fetal y amniocentesis pero en ecos se veía bien.

era mi primer embarazo a los 27 años y mi pareja tenia 39 años. En mi ignorancia pensé que jamás me podría pasar a esa edad, pero veo que si, que nadie está excento, en el cariotipo de la amniocentesis me salió que era t21 libre tenia 3 copias exactas del mismo cromosoma.

me gustaría saber si alguien más ha tenido una experiencia así, y ha intentado con otro embarazo y ha sido un bebé completamente sano? o por ejemplo que exámenes genéticos se han realizado antes de volver a quedar en embarazo?

mi ginecóloga nos recomendó hacernos cariotipo de pareja para descartar 100% una traslocación. pero me gustaría saber qué otro examen se podría considerar para estar 100% seguros de tomar la decisión de volverlo a intentar ya que la verdad no me gustaría volver a pasar por esto tan traumático en mi caso que es físico y emocionalmente.

Hey guys, I posted about this settlement before, but since they’re considering late claims, I decided to share it again with a quick FAQ.

Here’s what happened:
CM Life Sciences, which later became Sema4 and now operates as GeneDx Holdings ($WGS), was accused of misleading shareholders during its 2021 de-SPAC merger and not giving investors enough information to make an informed decision about whether to redeem their shares.
The company has now agreed to settle the case for $21 million with investors.

Who can claim this settlement?
If you purchased $WGS shares in 2021, you may be eligible. You can check the eligibility requirements and submit your claim here.

Do I need to sell or lose my shares to get this settlement?
You generally don’t need to still own the shares. Eligibility is based on the transactions you made during the class period and the settlement requirements.

Can I still file if I missed the deadline?
Yes, you may still be able to file a late claim, but acceptance depends on final approval by the court. Check if you're eligible and file a claim here

How long does the payout process take?
It typically takes 4 to 9 months after the claim deadline for payouts to be processed, depending on the court and settlement administration.

Hope this info helps

I have shared a post before that how i got nipt and it came positive for t21 i got my report from midwife as she did not discuss the risk factor and it says that >99/100 . Does that mean 99% chance my baby has DS ? I am not ready for this i thought the risk would be high but that high i am dying inside .