”By integrating clinical, computational, and experimental evidence, we propose a practical framework to improve TTN missense interpretation and support diagnoses." (5/5)

”Functional assays revealed that proline substitutions within Ig domain β-sheets impair protein folding, leading to aggregation and proteostasis disruption.” (4/5)

”Using allele frequency thresholds, exon usage data, segregation data and AlphaMissense, in line with ClinGen recommendations, we refined variant prioritization.” (3/5)

”In this international study, we focused on unsolved myopathy cases carrying a rare missense variant in trans with a truncating TTN variant. Across 30 patients, we observed a wide clinical spectrum from congenital to adult-onset disease.” (2/5)

A comprehensive framework for the interpretation of TTN missense variants - Genome Medicine Background Missense variants in TTN pose a major challenge in genetic diagnostics due to their high frequency in the general population, the large size of the gene, and the complex multidomain archite...

🚨Publication alert!🚨

First author Maria Francesca’s summary of the article:

"Missense variants in TTN remain one of the greatest challenges in neuromuscular genetics.” (1/5)

We see Rare Disease Day as an opportunity to show our support, but it is the research we do on rare muscle diseases that we hope will make a difference for these patients. For us, Rare Disease Day is every day! 💙 (5/5)

One of our main goals is to identify the genetic variants and possible pathogenetic mechanisms of the muscle disease to enable proper diagnosis and the development of eventual therapies. (4/5)

Receiving a diagnosis allows for a more accurate prognosis and choice of treatment, alleviating the psychological burden of the patients and their families. (3/5)

A delay in diagnosis is common for people with a rare disease. Of the patients with neuromuscular disorders, 40–60% remain without a genetic diagnosis. (2/5)

Today is Rare Disease Day. 🩷💚💙💜

Approximately 5% of the world's population is affected by a rare disease. #RareDiseaseDay is an important initiative for us, as nearly 90% of neuromuscular disorders are classified as rare diseases. (1/5)

@rarediseaseday.bsky.social

Are you discarding titin missense variants? You have no idea what you're missing! rdcu.be/e5ZXk #titin #musclediseases #rarediseases @myofinlab.bsky.social @folkhalsanresearch.bsky.social

Myofin’s research aims to identify the genetic variants causing neuromuscular disorders, to understand the structure and function of muscle and their alterations in disease, and to evaluate therapeutic interventions.

A rare disease is a medical condition that affects fewer than 1 in 2,000 people and often entails extensive, lifelong consequences.

To mark Rare Disease Day on 28 February we want to highlight the importance of Folkhälsan’s research on rare neuromuscular diseases – both for our researchers and for the people living with a rare neuromuscular condition.
@myofinlab.bsky.social

Swethaa from our lab, @myofinlab.bsky.social, presented on the advantages of rRNA-depleted RNA-seq over poly(A)+ selection for muscle and neuromuscular disease research at the #fiRNA #RNASalon meeting.

#MuscleResearch #RNAseq #NeuromuscularDisease

Today we participated in the Neuromuscular Club Meeting organised by the Finnish Neurological Society (Suomen Neurologinen Yhdistys). Marco, Ella, Giuliana, Jaakko and Swethaa presented during the day. 🌟

Thank you to the organisers! 💙

Helping patients is the ultimate purpose of Marco Savarese’s work Research group leader Marco Savarese enjoys his work and doesn’t go to sleep unless his inbox is empty. In the future, he hopes to see greater trust in science, a positive attitude toward new discover...

“Nothing is more rewarding than seeing new lab members arrive with curiosity and uncertainty, then develop the skills, confidence and independence to lead their own projects”, says @myofinlab.bsky.social Group Leader Marco Savarese in an interview for the Loimu Magazine:
www.loimu.fi/verkkolehden...

We truly appreciate this recognition and support from the university as it’s a wonderful encouragement for her research journey ahead. 🌟 (3/3)

Her PhD project focuses on understanding the molecular mechanisms behind titin-related myopathies, using multi-omics approaches such as transcriptomics, proteomics and translatomics. (2/3)

Very happy news from our lab! 🎉

We are grateful to the University of Helsinki (@helsinki.fi ) for awarding a research-funded doctoral position starting in January 2026. Swethaa has been selected for this position within the Clinical Research Doctoral Program. 👏 (1/3)

💡 These findings identify myosin as a molecular contributor to XLMTM – like what has been seen in nemaline myopathy – and highlight myosin as a potential drug target. (5/5)

💊 Blocking this overactive energy use with the myosin inhibitor mavacamten in a mouse model for XLMTM, partially restored the expression of proteins critical for muscle structure, contraction and energy balance. (4/5)

🔬 We found that myosin behaves abnormally in relaxed muscle from human XLMTM patients and dog/mouse models, preferring a structurally disordered and highly energy-consuming biochemical state. This increase in energy usage could contribute to muscle fatiguability. (3/5)

Fanny and Jenni’s summary of the article:

🧬 X-linked myotubular myopathy (XLMTM) is a rare, often fatal skeletal muscle disorder caused by mutations in the myotubularin gene. Its underlying disease mechanisms remain poorly understood. (2/5)

🚨Publication alert!🚨

This project was a huge collaborative effort during Fanny’s first year of her PhD, and Jenni’s postdoc in @droch.bsky.social lab at the University of Copenhagen. (1/5)

Closing the year with gratitude and looking ahead to continued scientific progress. Happy Holidays from Myofin! 🌟

”Beyond the numbers, we provide concrete guidance to make TTN variant interpretation clearer and more reliable. Our goal is to reduce uncertainty and support better diagnoses and research in rare diseases." (5/5)

”We also observed that 0.5% carried truncating variants in heart-expressed exons, but only 4% showed cardiomyopathy.” (4/5)

”Yet many cases remain unexplained, suggesting missing genetic contributors such as uncertain missense variants, variant combinations or more complex mechanisms.” (3/5)

”In over 18,000 individuals from the Solve-RD project, we found TTN truncating variants in 1.3% of all participants and in 3.8% of those with neuromuscular symptoms.” (2/5)