rs397516037

badMag 9.0

This is a splice donor variant variant in the MYBPC3 gene.

Key Literature Trait Associations

Hypertrophic Cardiomyopathy

The rs397516037 G>A variant introduces a premature stop codon (p.Gln1233Ter) in MYBPC3, the most commonly mutated gene in hypertrophic cardiomyopathy (HCM). ClinVar classifies this as Pathogenic with 2-star review status based on submissions from seven independent European molecular genetics laboratories, all concordantly rating it pathogenic with no conflicts. The variant has been identified in multiple European cohorts including a Hungarian series where MYBPC3 p.Gln1233Ter was found in 12 of 242 index HCM patients (5%), comprising 36% of all pathogenic/likely-pathogenic variants together with two other MYBPC3 truncating mutations, suggesting a possible central-European founder effect. Truncating MYBPC3 variants cause protein haploinsufficiency and are associated with variable age of o...

Sepp R et al. “The Genetic Architecture of Hypertrophic Cardiomyopathy in Hungary: Analysis of 242 Patients with a Panel of 98 Genes.” Diagnostics (basel, Switzerland) (2022)
Allele A
OR —
p —
N 242
Candidate gene study
Hungarian (European)
Helms AS et al. “Spatial and Functional Distribution of MYBPC3 Pathogenic Variants and Clinical Outcomes in Patients With Hypertrophic Cardiomyopathy.” Circulation. Genomic and Precision Medicine (2020)
Allele A
OR —
p —
N 4,756
Preliminary work
multi-ancestry
Chumakova A et al. “Application of RNA-seq for single nucleotide variation identification in a cohort of patients with hypertrophic cardiomyopathy.” Scientific Reports (2025)
Allele A
OR —
p —
N 48
Candidate gene study
Russian (European)
Salakhov RR et al. “Application of Long-Read Nanopore Sequencing to the Search for Mutations in Hypertrophic Cardiomyopathy.” International Journal of Molecular Sciences (2022)
Allele A
OR —
p —
N 4
Candidate gene study
Russian (European)
Filatova EV et al. “[No Effect of the p.Arg230His Variant Of The VCL Protein on the Course of the Hypertrophic Cardiomyopathy In Russian Family Carrying The p.Gln1233Ter Pathogenic Variant In The MYBPC3 Gene].” Kardiologiia (2023)
Allele A
OR —
p —
N 4
Candidate gene study
Russian (European)
▶

ClinVar annotation

Pathogenic★★★☆
28 submitters37 publications

Cardiomyopathy (CMYO); Cardiovascular phenotype; Dilated cardiomyopathy 1I (CMD1I); Hypertrophic cardiomyopathy; Hypertrophic cardiomyopathy 4; Left ventricular hypertrophy; Left ventricular noncompaction 10 (LVNC10); Primary familial hypertrophic cardiomyopathy (HCM); See cases

View on ClinVar →

Gene information from NCBI Gene. Variant classifications from ClinVar.

Community Wiki

No community notes yet for this variant. Sign in to start one.

Comments

Sign in to join the discussion.

Loading comments…