Andrew Glazer

Editing stem cell genomes at scale to measure variant effects in diverse cell and genetic contexts Multiplexed assays of variant effect (MAVEs) systematically measure variant function but have been limited to cancer cell lines rather than disease-relevant cell types. We developed saturation genome ...

The effects of genetic variants primarily occur in differentiated cells meaning we need to access these cell types to measure variant effects for most disease genes. We developed saturation genome editing in stem cells (iPSC-SGE) to enable phenotyping in diverse genetic and cell contexts at scale!

The Mosley lab is seeking creative postdoctoral fellows interested in applying innovative population-based genomic and informatics approaches to translate genetics into clinical settings.

labs.utsouthwestern.edu/mosley-lab/p...

www.utsouthwestern.edu/research/pos...

🧪🧬🖥️

Thank you @amglazer.bsky.social for the exciting opportunity to collaborate! Since then, we've provided functional evidence supporting the VUS reclassification in children with abnormal sodium #ionchannel function at Sydney Children’s Hospital.

This was a collaborative project led by Matthew O'Neill and Joanne Ma and co-supervised by me, Jamie Vandenberg, and @chaiannng.bsky.social. Link: academic.oup.com/eurheartj/ad... [4/4]

Variants with severe loss-of-function had ~25% penetrance & 501x increased odds of BrS. Normal-function variants had lower risk. This work stratifies SCN5A variants into low-risk vs high-risk categories, aiding diagnosis & management for patients & families. [3/4]

Using our calibrated automated patch clamp assay, we identified 146 abnormal function variants and reclassified 110 VUS. [2/4]

📝 Excited to share our latest work, now out at European Heart Journal! We studied 252 SCN5A variants previously found in patients with Brugada Syndrome, an inherited arrhythmia disorder linked to sudden cardiac death. [1/4]

Congrats to Matthew O'Neill for winning an American Heart Association Early Career award for our work on functional studies of SCN5A variants from patients with Brugada syndrome!

So excited about this new work from our CardioVar consortium out this week in Science led by the amazing Daniel Tabet and @fritzroth.bsky.social.

www.science.org/doi/10.1126/

I gave my daughter C, A, and T cards to spell "cat." She grabbed a G and added it to the mix. Is she hinting at a future career in genetics? 🧬 🐾

Creating an atlas of variant effects to resolve variants of uncertain significance and guide cardiovascular medicine - Nature Reviews Cardiology In this Review, Roden and co-workers describe how multiplexed assays of variant effects can be used for high-throughput functional assessment of nearly all coding variants in a target sequence to impr...

🧬 Out this month in Nature Reviews Cardiology: A powerful look at how multiplexed assays of variant effects (MAVEs) are reshaping our understanding of cardiovascular disease genetics. Contributors include members of the AVE Alliance.
📑 www.nature.com/articles/s41...
#Cardiology #FunctionalGenomics

The 9th Annual Mutational Scanning Symposium will be held in Melbourne, Australia March 25-27, 2026 🌟 #VariantEffect26
www.mss2026.org Registration will open soon!!!!

Landscapes of missense variant impact for human superoxide dismutase 1 SOD1 variants cause the motor neuron disease amyotrophic lateral sclerosis. Axakova et al. functionally assay ∼86% of all possible SOD1 missense variants, producing a variant-effect map resource that ...

📣New today!
📄Landscapes of missense variant impact for human superoxide dismutase 1
🧑‍🤝‍🧑 @axakova.bsky.social @fritzroth.bsky.social & co

Creating an atlas of variant effects to resolve variants of uncertain significance and guide cardiovascular medicine - Nature Reviews Cardiology In this Review, Roden and co-workers describe how multiplexed assays of variant effects can be used for high-throughput functional assessment of nearly all coding variants in a target sequence to impr...

And follow it up with @natrevcardiol.nature.com's review on the application of MAVEs in cardiology by @amglazer.bsky.social et al.

Creating an atlas of variant effects to resolve variants of uncertain significance and guide cardiovascular medicine
go.nature.com/3JOJYc3
rdcu.be/eFmoe

Link: www.nature.com/articles/s41... Thanks to CardioVar coauthors @fritzroth.bsky.social Dan Roden, Dan Tabet, Vicki Parikh, Euan Ashley, Calum MacRae, and more!

📝Check out our review “Creating an atlas of variant effects to resolve variants of uncertain significance and guide cardiovascular medicine”, out in @natrevcardiol.nature.com. We review the use of Multiplexed Assays of Variant Effect and variant effect predictors in cardiovascular disease.

Redefining the Genetic Architecture of Hypertrophic Cardiomyopathy: Role of Intermediate Effect Variants | Circulation Background: Hypertrophic cardiomyopathy (HCM) is a genetically heterogeneous disorder primarily linked to rare variants in sarcomere genes, though recently certain non-sarcomeric genes have emerged as...

Our study on HCM intermediate effect variants (IEVs) is out today in Circulation, led by Juan Pablo Ochoa, Soledad García Hernandez and Luis De la Higuera Romero.

IEVs are low frequency/penetrance variants with moderate effects sizes (OR:5-10).
www.ahajournals.org/doi/10.1161/...

#ESCcongress 🧬🫀

Having some summer fun...Glazer Lab Olympics! Our lab competed in 6 lab-themed events.

More smiles to share with you; this time, Andrew Glazer and Richard Dolder from the Glazer Lab at Vanderbilt University Medical Center.

New blog: timothysyndrome.org/research/det...

#CACNA1C #RareDisease #Research @amglazer.bsky.social @vanderbilt.edu

My wife and I had a lovely time in Spain, including the excellent #VariantEffect25 meeting!

Our "Atlas of Variant Effects 2030 Roadmap" is live: zenodo.org/records/1542...

1/n

Polygenic score for height could improve diagnosis for children with short stature: study About 30% of children with short stature do not have a definitive diagnosis, leading to extra testing and anxiety.

Congratulations, John Shelley.

news.vumc.org/2025/04/25/p...

#VUMCMSTP #VUMCDBMI
#PopGen #Bioinformatics #Genomics 🧬🖥️🧪

Guidelines for releasing a variant effect predictor - Genome Biology Computational methods for assessing the likely impacts of mutations, known as variant effect predictors (VEPs), are widely used in the assessment and interpretation of human genetic variation, as well...

New paper out in Genome Biology! 🎉
We lay out best-practice guidelines for releasing variant effect predictors, developed through the Atlas of Variant Effects Alliance @varianteffect.bsky.social

Open, interpretable, and clinically useful VEPs are the goal.

📄 doi.org/10.1186/s130...

Characterizing trends in clinical genetic testing: A single-center analysis of EHR data from 1.8 million patients over two decades A study of electronic health records (EHRs) from 1.8 million patients at Vanderbilt University Medical Center highlights the growing role of genetic testing in clinical medicine. The study demonstrate...

📣New from Bastarache & co
📄Characterizing trends in clinical genetic testing: A single-center analysis of EHR data from 1.8 million patients over two decades

Saturation genome editing of RNU4-2 reveals distinct dominant and recessive neurodevelopmental disorders Recently, de novo variants in an 18 nucleotide region in the centre of RNU4-2 were shown to cause ReNU syndrome, a syndromic neurodevelopmental disorder (NDD) that is predicted to affect tens of thous...

🚨I could not be more excited to share our new preprint on saturation genome editing of the small nuclear RNA (snRNA) RNU4-2:
www.medrxiv.org/content/10.1...

A super fun collaboration with incredible duo @gregfindlay.bsky.social @joachimdejonghe.bsky.social from @crick.ac.uk
🧬🖥️🩺

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Combined RNA Splicing and Patch-Clamp Analysis Reveal Pathogenicity of Splice-Altering Variants in KCNH2-Related LQTS | Circulation: Genomic and Precision Medicine

I am pleased to share this @ahajournals.bsky.social CircGen paper. It is a team effort. I hope we have provided valuable insights on how KCNH2 variant that alters splicing and causes a large in-frame deletion can lead to a dominant negative effect of Kv11.1 K+ #ionchannel function.

It was great to attend the ACMG clinical genetics meeting for the first time, including a fun session on advances in cardiovascular genomics.

Cohort-scale automated patch clamp data improves variant classification and penetrance stratification for SCN5A-Brugada Syndrome Background: Brugada Syndrome (BrS) is an inherited arrhythmia disorder that causes an elevated risk of sudden cardiac death. Approximately 20% of patients with BrS have rare variants in SCN5A, which e...

This was a collaborative project led by Matthew O'Neill and Joanne Ma and co-supervised by Jamie Vandenberg, @chaiannng.bsky.social and myself. Check out our preprint for more details! www.medrxiv.org/content/10.1... [7/7]

Our data helps stratify SCN5A variants in BrS patients into normal-function "bystander" variants with low BrS risk and loss-of-function variants with higher BrS risk. We hope the dataset will improve diagnosis and clinical management of BrS patients and their families. [6/7]

Disease risk was proportional to the severity of loss-of-function; variants with Z ≤ -6 had a penetrance of 24.5% and an odds ratio of 501 for BrS. [5/7]