Discovery of a cryptic founder variant in MYBPC3 associated with hypertrophic cardiomyopathy by promoting the most frequent natural missplicing events

  1. Gallego Delgado, M 2
  2. Torrado, M 3
  3. Perez Barbeito, M 4
  4. Lorenzo Hernandez, S L 1
  5. Rodriguez Diego, S 2
  6. Garcia Berrocal, B 1
  7. Garcia Hernandez, S 4
  8. Garcia Monsalvo, M 2
  9. Garcia Salgado, M J 1
  10. Maneiro Pampin, E 4
  11. Alvarez Martinez, C 2
  12. Ochoa, J P 4
  13. Sanchez, P L 2
  14. Isidoro Garcia, M 1
  15. Villacorta, E 2
  1. 1 Complejo Asistencial Universitario de Salamanca, Clinical Biochemistry , Salamanca ,
  2. 2 Complejo Asistencial Universitario de Salamanca, Cardiology , Salamanca ,
  3. 3 University of A Coruña. Biomedical Research Institute of A Coruña, Cardiovascular Research Group , A Coruna ,
  4. 4 Health in Code , A Coruna ,
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Journal:
European Heart Journal

ISSN: 0195-668X,  1522-9645

Year of publication: 2024

Volume: 45

Issue: Supplement 1

Type: Article

DOI: 10.1093/EURHEARTJ/EHAE666.2019 GOOGLE SCHOLAR

More publications in: European Heart Journal

Abstract

MYBPC3 splicing errors are a common cause of hypertrophic cardiomyopathy (HCM). Most known actionable intronic variants are located near exons. However, genetic variants in deep intronic regions are also emerging as casuals factors of HCM. The previously undescribed variant MYBPC3 (NM_000256.3):c.2308+227G>A is not reported in gnomAD or dbSNP but is overrepresented in a cohort of probands with HCM from the same geographical area. This led us to suspect its clinical relevance despite the very low probability of being splice-altering as assigned by SpliceAI (Δ score = 0.03).