In this preprint, we present two complementary approaches for resolving variants of uncertain significance (VUS) in the gene TSC2. VUS are a common issue for individuals who receive genetic testing for a suspected genetic condition. Resolving VUS is important! 1/12.

RT @SAOscience: "Because aspects of human brain development are difficult to model in animals," @hcmefford & team developed brain organoids….

RT @rebeccasugar: If you missed our concert for @TrevorProject it's now available to watch (link in reply) and the donation link is still l….

@PeterCrino Also, Jacob and Ryleigh are making the trip to Chicago in spirit to act as a constant reminder of the importance of continuing to study TSC1 and TSC2

As a slight tangent, I want to thank @PeterCrino for encouraging me to apply for the AES JIA award back circa 2021 or so. Their generous funding is the reason I was able to join the TSC field. Planning to stick around as long as possible!.

"The TSC brain is an inflamed brain", and there is a need to harmonize omics data from different labs to facilitate a meta analysis that might yield novel druggable targets.

Peter Crino somehow managed to give a whirlwind overview summarizing the state of the field in terms of epileptic networks and cellular anatomy. An incomplete list of take-home messages: microtubers are under studied, slice ephys needs to be done on more resected tissue,.

Brendan Manning gave an incredible talk on metabolism in the context of mTOR pathway dysregulation and rapamycin treatment. I think the field, myself included, need to think a lot more about cellular metabolism in addition to cellular processes we tend to focus on.

Rebecca Ihrie gave a tour de force talk that i can't possibly do justice summarizing on this platform. So many interesting insights ranging from proteomics, phospho-proteomics, and epigenetics. Highly recommend checking out the recent papers from her lab.

Tommy Li presented his work on the two hit model that he studied in both organoids and clinical samples. Particularly interesting work using the new serial imaging technique to stain 1 sample for many targets. Lots of fascinating mechanistic insights!.

Morgan Moser presented on gene therapy approaches. Very cool method to miniaturize a TSC2 expression construct to fit within the packaging limits of AAV delivery platform. I'll be keeping 👀 peeled to see where this work goes over the coming years!.

Aynara Wulsin presented on using standard terms derived from the electronic health record to enable natural history study, genotype phenotype correlation, and other studies in TSC. This method could prove very fruitful, but needs to overcome bottleneck of manual curation of EHR.

As someone who has trained in mostly germline rare genetic epilepsies, the idea that a mosaic variant of quite low frequency can give rise to same or similar phenotype as a germline variant is very interesting and will be something i will be pondering going forward.

I really enjoy Clara Chung talking about deep sequencing with a gene panel. It turns out that many, though certainly not all, no mutation identified (NMI) cases are actually mosaic and require 500+X coverage to detect. Sometimes you even need affected tissue like a tuber to solve.

Lots of great talks were given at this year's conference. I'll highlight a few, please bear in mind that these were of particular interest to me and my inherent biases and by no means exhaustive.

First, the TSC community is very welcoming. I am still quite new, and everyone has been very kind and encouraging. I am heading home feeling very inspired to redouble my efforts to help resolve variants of uncertain significance (VUS) in TSC2.

The 2025 TSC International Conference organized by the amazing @tscalliance just wrapped up. An absolutely incredible conference, so much science packed into two days. In this thread I am going to post some thoughts from the conference. 1/?.

RT @rebeccasugar: Please join us from 7-9pPST JUNE 29 for a free virtual concert fundraiser for @trevorproject 🧡streaming live from my inst….

RT @curechd2: 🎉Coalition to Cure CHD2 has granted €100,000 to Dr. Nael Nadif Kasri to advance personalized medicine for CHD2-related disord….

RT @plasmidsaurus: This is exactly what happens inside our sequencing machines. 😌

RT @YannCPhD: Excited to share our latest study from the Manning Lab. We have developed and characterized a novel mouse model lacking the f….