RBM20
Chr 10ADRNA binding motif protein 20
This highly constrained gene encodes an RNA-binding protein that regulates alternative splicing of cardiac structural proteins including titin, specifically binding intronic sequences to promote exon skipping during cardiac development. Mutations cause autosomal dominant dilated cardiomyopathy (cardiomyopathy, dilated, 1DD), which primarily affects cardiac muscle function. The gene's high constraint against loss-of-function variants (pLI 0.99, LOEUF 0.30) suggests intolerance to protein-disrupting mutations.
Limited evidence — not for standalone diagnostic reporting
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
500 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 36 | 0 | 1 | 0 | 37 |
Likely Pathogenic | 17 | 1 | 3 | 0 | 21 |
VUS | 12 | 231 | 13 | 3 | 259 |
Likely Benign | 0 | 14 | 43 | 112 | 169 |
Benign | 0 | 2 | 1 | 0 | 3 |
Conflicting | — | 10 | |||
| Total | 65 | 248 | 61 | 115 | 499 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RBM20 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools