NM_001134363.3(RBM20):c.1603G>A (p.Val535Ile) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 30, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000619976.4

Allele description [Variation Report for NM_001134363.3(RBM20):c.1603G>A (p.Val535Ile)]

NM_001134363.3(RBM20):c.1603G>A (p.Val535Ile)

Gene:

RBM20:RNA binding motif protein 20 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q25.2

Genomic location:

Preferred name:

NM_001134363.3(RBM20):c.1603G>A (p.Val535Ile)

Other names:

p.V535I:GTC>ATC

HGVS:

NC_000010.11:g.110797583G>A
NG_021177.1:g.158187G>A
NM_001134363.3:c.1603G>AMANE SELECT
NP_001127835.2:p.Val535Ile
LRG_382t1:c.1603G>A
LRG_382:g.158187G>A
NC_000010.10:g.112557341G>A
NM_001134363.1:c.1603G>A
NM_001134363.2:c.1603G>A

Protein change:

V535I

Links:

dbSNP: rs183007628

NCBI 1000 Genomes Browser:

rs183007628

Molecular consequence:

NM_001134363.3:c.1603G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000736572	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jan 30, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20590677, 22466703, 35470680 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000736572

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jan 30, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Identification of novel mutations in RBM20 in patients with dilated cardiomyopathy.

Li D, Morales A, Gonzalez-Quintana J, Norton N, Siegfried JD, Hofmeyer M, Hershberger RE.

Clin Transl Sci. 2010 Jun;3(3):90-7. doi: 10.1111/j.1752-8062.2010.00198.x.

PubMed [citation]

PMID:: 20590677
PMCID:: PMC2898174

RBM20, a gene for hereditary cardiomyopathy, regulates titin splicing.

Guo W, Schafer S, Greaser ML, Radke MH, Liss M, Govindarajan T, Maatz H, Schulz H, Li S, Parrish AM, Dauksaite V, Vakeel P, Klaassen S, Gerull B, Thierfelder L, Regitz-Zagrosek V, Hacker TA, Saupe KW, Dec GW, Ellinor PT, MacRae CA, Spallek B, et al.

Nat Med. 2012 May;18(5):766-73. doi: 10.1038/nm.2693.

PubMed [citation]

PMID:: 22466703
PMCID:: PMC3569865

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000736572.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The p.V535I variant (also known as c.1603G>A), located in coding exon 6 of the RBM20 gene, results from a G to A substitution at nucleotide position 1603. The valine at codon 535 is replaced by isoleucine, an amino acid with highly similar properties. This variant was reported in a patient with dilated cardiomyopathy (DCM) who also carried an alteration in LDB3, and was also detected in association with DCM in an additional cohort; however, details were limited (Li D et al, Clin Transl Sci 2010 Jun; 3(3):90-7; Smith E et al. J Am Heart Assoc. 2022 May;11(9):e024501). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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