RBM20

RNA binding motif protein 20, the group of RNA binding motif containing

Basic information

Region (hg38): 10:110644335-110839468

Links

ENSG00000203867 ∙ NCBI:282996 ∙ OMIM:613171 ∙ HGNC:27424 ∙ Uniprot:Q5T481 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
• dilated cardiomyopathy 1DD (Strong), mode of inheritance: AD
• dilated cardiomyopathy 1DD (Definitive), mode of inheritance: AD
• dilated cardiomyopathy 1DD (Strong), mode of inheritance: AD
• hypertrophic cardiomyopathy (Limited), mode of inheritance: AD
• dilated cardiomyopathy (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, dilated, 1DD	AD	Cardiovascular	Surveillance (eg, with echocardiography and electrocardiography), preventive measures and medical management may help decrease morbidity; Cardiac transplantation has been described	Cardiovascular	19712804; 20590677; 21846512

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RBM20 gene.

• Dilated cardiomyopathy 1DD (1313 variants)
• Cardiovascular phenotype (534 variants)
• not provided (354 variants)
• not specified (236 variants)
• Cardiomyopathy (114 variants)
• Primary dilated cardiomyopathy (38 variants)
• Inborn genetic diseases (21 variants)
• RBM20-related condition (9 variants)
• Primary familial dilated cardiomyopathy (7 variants)
• Primary familial hypertrophic cardiomyopathy (7 variants)
• Dilated Cardiomyopathy, Dominant (6 variants)
• Hypertrophic cardiomyopathy (6 variants)
• Dilated cardiomyopathy 1A (5 variants)
• Long QT syndrome (4 variants)
• Arrhythmogenic right ventricular cardiomyopathy (3 variants)
• Ventricular fibrillation, paroxysmal familial, type 1 (2 variants)
• Left ventricular noncompaction cardiomyopathy (2 variants)
• Hypertrophic cardiomyopathy;Cardiac arrest (1 variants)
• Arrhythmogenic right ventricular cardiomyopathy;Long QT syndrome (1 variants)
• Familial dilated cardiomyopathy and peripheral neuropathy (1 variants)
• Ventricular tachycardia;Pulmonary valve stenosis (rare) (1 variants)
• Heart failure (1 variants)
• Cardiomyopathy;Primary dilated cardiomyopathy (1 variants)
• Dilated cardiomyopathy 1S (1 variants)
• Conduction disorder of the heart (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RBM20 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			13	337	5	355
missense	3	8	591	68	9	679
nonsense	1	2	29	1		33
start loss						0
frameshift		3	37			40
inframe indel			25			25
splice donor/acceptor (+/-2bp)			9			9
splice region			14	29	1	44
non coding			64	95	49	208
Total	4	13	768	501	63

Variants in RBM20

This is a list of pathogenic ClinVar variants found in the RBM20 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-110644424-T-C		Dilated cardiomyopathy 1DD	Uncertain significance (Jan 12, 2018)
10-110644436-C-T		not specified	Likely benign (Jan 26, 2016)
10-110644439-G-T		not specified	Uncertain significance (Feb 16, 2015)
10-110644447-C-T		not specified	Likely benign (Dec 27, 2017)
10-110644449-C-T		not specified	Likely benign (Oct 27, 2022)
10-110644453-G-T		Cardiovascular phenotype	Uncertain significance (Oct 04, 2021)
10-110644454-C-T		Cardiovascular phenotype	Uncertain significance (Mar 28, 2020)
10-110644458-G-T		Cardiomyopathy	Uncertain significance (Nov 27, 2019)
10-110644459-T-C		Dilated cardiomyopathy 1DD • Cardiomyopathy	Uncertain significance (Aug 03, 2022)
10-110644461-C-T		Dilated cardiomyopathy 1DD • Cardiovascular phenotype	Likely benign (Jan 22, 2024)
10-110644468-C-T		Dilated cardiomyopathy 1DD	Likely benign (Oct 30, 2023)
10-110644469-A-T		Dilated cardiomyopathy 1DD • Cardiovascular phenotype	Likely benign (Sep 30, 2023)
10-110644470-G-A		Dilated cardiomyopathy 1DD • Cardiovascular phenotype	Uncertain significance (Aug 04, 2022)
10-110644473-A-G			Uncertain significance (Jun 05, 2019)
10-110644473-A-T			Uncertain significance (Dec 05, 2017)
10-110644474-T-C		Cardiovascular phenotype	Uncertain significance (Dec 05, 2019)
10-110644474-T-G		Dilated cardiomyopathy 1DD	Likely benign (Sep 17, 2022)
10-110644479-C-T		Dilated cardiomyopathy 1DD	Uncertain significance (Dec 06, 2021)
10-110644481-G-C		Dilated cardiomyopathy 1DD • Cardiovascular phenotype	Conflicting classifications of pathogenicity (Dec 28, 2023)
10-110644486-C-T			Uncertain significance (Mar 05, 2015)
10-110644489-A-T		Dilated cardiomyopathy 1DD	Uncertain significance (Sep 15, 2023)
10-110644490-C-A		Cardiovascular phenotype • Dilated cardiomyopathy 1DD	Conflicting classifications of pathogenicity (Dec 27, 2023)
10-110644490-C-T		Cardiovascular phenotype	Likely benign (Oct 26, 2023)
10-110644496-C-G		Dilated cardiomyopathy 1DD • Cardiovascular phenotype	Conflicting classifications of pathogenicity (Nov 06, 2023)
10-110644497-G-A		Dilated cardiomyopathy 1DD • Cardiovascular phenotype	Uncertain significance (Jan 27, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RBM20	protein_coding	protein_coding	ENST00000369519	14	195073

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.990	0.0105	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.67	543	664	0.818	0.0000376	7995
Missense in Polyphen		184	246.54	0.74633		2879
Synonymous	2.10	226	270	0.837	0.0000165	2450
Loss of Function	5.22	7	44.6	0.157	0.00000218	575

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: RNA-binding protein that acts as a regulator of mRNA splicing of a subset of genes involved in cardiac development. Regulates splicing of TTN (Titin). {ECO:0000269|PubMed:22466703}.

Intolerance Scores

• rvis_EVS: 1.02
• rvis_percentile_EVS: 90.98

Haploinsufficiency Scores

• pHI: 0.359

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.140

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Rbm20
• Phenotype: homeostasis/metabolism phenotype; muscle phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Gene ontology

• Biological process: mRNA processing;heart development;RNA splicing;positive regulation of RNA splicing
• Cellular component: nucleus
• Molecular function: RNA binding;zinc ion binding