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Andrew Glazer @amglazer.bsky.social · 15d

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? 🧬 🐾

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Reposted by Andrew Glazer

Atlas of Variant Effects Alliance @varianteffect.bsky.social · 19d

🧬 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

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...

www.nature.com

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Reposted by Andrew Glazer

Atlas of Variant Effects Alliance @varianteffect.bsky.social · 23d

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

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Reposted by Andrew Glazer

The American Journal of Human Genetics @ajhgnews.bsky.social · 23d

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

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 ...

www.cell.com

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Reposted by Andrew Glazer

Nature Reviews Genetics @natrevgenet.nature.com · 29d

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

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...

go.nature.com

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Andrew Glazer @amglazer.bsky.social · Sep 3

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!

Andrew Glazer @amglazer.bsky.social · Sep 3

📝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.

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Reposted by Andrew Glazer

Roddy Walsh 🇪🇺 🇺🇦 @roddywalsh.bsky.social · Aug 29

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 🧬🫀

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...

www.ahajournals.org

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Andrew Glazer @amglazer.bsky.social · Jul 16

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

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Reposted by Andrew Glazer

Timothy Syndrome Alliance (TSA) @cacna1c.bsky.social · Jun 18

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

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Andrew Glazer @amglazer.bsky.social · May 25

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

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Reposted by Andrew Glazer

Doug Fowler @dougfowler.bsky.social · May 15

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

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Atlas of Variant Effects 2030 Roadmap: resolving human variants of uncertain significance

At the Clinical Atlas of Variant Effects meeting (CLAVE meeting, July 2024, Pittsburgh USA), we developed recommendations for a draft atlas that can be realized by 2030, with a focus on empowering gen...

zenodo.org

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Reposted by Andrew Glazer

Jonathan Mosley @jdmosley-moses.bsky.social · Apr 26

Congratulations, John Shelley.

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

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

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.

news.vumc.org

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Reposted by Andrew Glazer

Joe Marsh @jmarshlab.bsky.social · Apr 15

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...

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...

doi.org

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Reposted by Andrew Glazer

The American Journal of Human Genetics @ajhgnews.bsky.social · Apr 17

📣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

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...

www.cell.com

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Reposted by Andrew Glazer

Nicky Whiffin @nickywhiffin.bsky.social · Apr 11

🚨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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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...

www.medrxiv.org

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Reposted by Andrew Glazer

Chai Ann Ng @chaiannng.bsky.social · Mar 27

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.

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

www.ahajournals.org

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Andrew Glazer @amglazer.bsky.social · Mar 22

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

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Andrew Glazer @amglazer.bsky.social · Mar 20

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]

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...

www.medrxiv.org

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Andrew Glazer @amglazer.bsky.social · Mar 20

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]

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Andrew Glazer @amglazer.bsky.social · Mar 20

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]

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Andrew Glazer @amglazer.bsky.social · Mar 20

Out of 252 variants, 146 were functionally abnormal (Z ≤ -2), with 100 showing severe loss-of-function (Z ≤ -4). Functional evidence allowed us to reclassify 110 of 225 VUS: 104 to likely pathogenic and 6 to likely benign. [4/7]

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Andrew Glazer @amglazer.bsky.social · Mar 20

Using automated patch clamp, we analyzed 252 SCN5A variants from a previously published cohort of 3,335 BrS cases. We previously showed this assay performs well on benign/pathogenic controls. The controls were used to calculate normalized Z-scores for the 252 variants. [3/7]

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Andrew Glazer @amglazer.bsky.social · Mar 20

Brugada Syndrome (BrS) is an inherited arrhythmia disorder with an elevated risk of sudden cardiac death. ~20% of patients have rare variants in the cardiac sodium channel gene SCN5A. Challenges include Variants of Uncertain Significance (VUS) and incomplete penetrance. [2/7]

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Andrew Glazer @amglazer.bsky.social · Mar 20

🧵 I’m excited to share our latest preprint! We studied 252 SCN5A variants found in patients with Brugada Syndrome by automated patch clamp. [1/7]

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