Evidence map›Paper›PMID 41357762›Full record

ArticleHuman mutation2025

Reclassification of VUS Using ACMG/AMP Criteria Adapted for Sarcomeric Genes Related to Hypertrophic Cardiomyopathy: Resolution Rate and Considerations.

Silvia Caroselli, Giulia Corona, Marco Fabiani, Martina Manzoni, Caterina Micolonghi, Camilla Savio, Aldo Germani, Stefania Bragliola, Valeria Maselli, Speranza Rubattu and 6 more

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Article in Human mutation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Silvia CaroselliDepartment of Experimental Medicine, Sapienza University of Rome, Rome, Italy.ORCID 0009-0009-2496-6647
Giulia CoronaUnità di Genetica Cardiovascolare, Centro Cardiologico Monzino IRCCS, Milan, Italy.ORCID 0009-0009-7041-5520
Marco FabianiDepartment of Experimental Medicine, Sapienza University of Rome, Rome, Italy.ORCID 0000-0002-8763-0114
Martina ManzoniUnità di Genetica Cardiovascolare, Centro Cardiologico Monzino IRCCS, Milan, Italy.ORCID 0000-0003-0861-9951
Caterina MicolonghiDepartment of Experimental Medicine, Sapienza University of Rome, Rome, Italy.ORCID 0000-0002-4275-0032
Camilla SavioUOD Genetica Medica, Sant'Andrea University Hospital, Rome, Italy.ORCID 0009-0005-5944-2588
Aldo GermaniDepartment of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.ORCID 0000-0001-5108-3924
Stefania BragliolaDepartment of Experimental Medicine, Sapienza University of Rome, Rome, Italy.ORCID 0009-0007-8499-6077
Valeria MaselliDepartment of Experimental Medicine, Sapienza University of Rome, Rome, Italy.ORCID 0000-0001-9180-6664
Speranza RubattuDepartment of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.ORCID 0000-0001-5921-7368
Beatrice MusumeciDepartment of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.ORCID 0000-0003-4872-7981
Giacomo TiniDepartment of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.ORCID 0000-0001-8520-152X
Vincenzo ViscoUOD Genetica Medica, Sant'Andrea University Hospital, Rome, Italy.ORCID 0000-0001-5067-3121
Simona PetrucciUOD Genetica Medica, Sant'Andrea University Hospital, Rome, Italy.ORCID 0000-0003-3400-4547
Valeria NovelliUnità di Genetica Cardiovascolare, Centro Cardiologico Monzino IRCCS, Milan, Italy.ORCID 0000-0002-4859-0826
Maria PianeUOD Genetica Medica, Sant'Andrea University Hospital, Rome, Italy.ORCID 0000-0001-8569-247X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Genetic testing is valuable to confirm molecular diagnosis in nearly 60% of cases suspected of hypertrophic cardiomyopathy (HCM). However, the interpretation of variants, especially those of uncertain significance (VUSs), remains challenging for laboratories and clinicians. In April 2024, the ClinGen Cardiomyopathy Variant Curation Expert Panel (VCEP) adapted the ACMG/AMP criteria for eight of the sarcomeric genes ( Methods: Here, two groups of curators reinterpreted variants with the most recent data using the Cardiomyopathy VCEP specifications until a consensus was reached. To streamline the process, we created a semiautomated decision support tool based on these gene-specific rules. Results: The application of the Cardiomyopathy VCEP specifications resulted in the reclassification of 17.4% ( Conclusion: Using gene-specific ACMG/AMP criteria reduces the rate of VUS, increasing diagnostic yield, and informing clinical management in the context of HCM. Nonetheless, ongoing efforts to generate evidence and promote standardization remain essential to improve variant interpretation.

Indexed as

Cardiomyopathy, HypertrophicGenetic TestingGenetic VariationSarcomeresFemaleGenetic Predisposition to DiseaseHumansMaleMiddle AgedMutationRetrospective Studies

Identifiers

PMID41357762
PMCPMC12681420

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.