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

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 (MYH7, MYBPC3, TNNI3, TNNT2, TPM1, ACTC1, MYL2, and MYL3), providing a refined framework for variant interpretation in these genes. This retrospective study re-evaluated 69 VUSs identified in 84 HCM patients between 2017 and 2024, aiming to resolve uncertainty and reduce the VUS rate.

Methods

Here,

SUBMITTER: Caroselli S 

PROVIDER: S-EPMC12681420 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature