Welcome to the Gene Scene! Each week, we will explore a gene from the ACMG Secondary Findings list—genes identified by the American College of Medical Genetics and Genomics as having clear, actionable health implications. These genes are included because they’re linked to serious but preventable or manageable conditions when identified early. Here, we focus on the condition that led to the gene’s inclusion on the list, providing clear, relevant information that supports your clinic. To subscribe to the Gene Scene, contact your local GSL or send a request to info@ambrygen.com.
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Clinical Phenotype Summary:
The MYBPC3 gene, located on chromosome 11p11.2, encodes the cardiac myosin-binding protein C. Pathogenic variants in this gene have been associated with a spectrum of MYBPC3-related cardiomyopathies, including hypertrophic cardiomyopathy (HCM) and left ventricular noncompaction cardiomyopathy (LVNC), which can be inherited in an autosomal dominant or autosomal recessive fashion.
HCM is defined by unexplained left ventricular hypertrophy with increased septal or posterior wall thickness, often leading to:
- Early onset syncope
- Ventricular fibrillation
- Episodic chest pain
- Dyspnea
- Cardiac arrest
LVNC is characterized by excessive and prominent trabeculations of the left ventricle with deep intertrabecular recesses and a thickening of the endocardial noncompacted layer.
Variable expression and reduced penetrance are observed in heterozygous individuals. Autosomal recessive MYBPC3-related cardiomyopathy is typically more severe with an earlier age of onset, during adolescence through early adulthood, although some patients with neonatal-onset have also been reported.
Clinical Resources:
Understanding Your Positive Cardiomyopathy Genetic Test Result
Hereditary Cardiovascular Testing Counseling Aid
Ambry Knows Genes:
To read more about Ambry’s research on this gene. Visit the ‘Our Research’ dropdown on our website https://www.ambrygen.com/science.
Citations:
Wessels MW et al. Eur J Hum Genet, 2015 Jul;23:922-8 (PMID: 25335496)
Marian AJ et al. Circ Res, 2017 Sep;121:749-770 (PMID: 28912181)
Sedaghat-Hamedani F et al. Eur Heart J, 2017 Dec;38:3449-3460 (PMID: 29029073)
Ingles J et al. Circ Genom Precis Med, 2019 02;12:e002460 (PMID: 30681346)
van Waning JI et al. J Am Heart Assoc, 2019 12;8:e012993 (PMID: 31771441)
Allouba M et al. Eur Heart J, 2023 Dec;44:5146-5158 (PMID: 37431535)
Ambry Genetics Gene-Disease Validity Scheme
Each week, we explore a gene from the ACMG Secondary Findings list—genes identified by the American College of Medical Genetics and Genomics as having clear, actionable health implications. These genes are included because they’re linked to serious but preventable or manageable conditions when identified early.
To learn more about the ACMG Secondary Findings list, click here.
To read all previous Gene Scene emails, click here.
