NM_002230.4(JUP):c.1730G>A (p.Arg577His) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 6, 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:: RCV003164347.2

Allele description [Variation Report for NM_002230.4(JUP):c.1730G>A (p.Arg577His)]

NM_002230.4(JUP):c.1730G>A (p.Arg577His)

Gene:

JUP:junction plakoglobin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.2

Genomic location:

Preferred name:

NM_002230.4(JUP):c.1730G>A (p.Arg577His)

HGVS:

NC_000017.11:g.41758442C>T
NG_009090.2:g.33271G>A
NM_001352773.2:c.1730G>A
NM_001352774.2:c.1730G>A
NM_001352775.2:c.1730G>A
NM_001352776.2:c.1730G>A
NM_001352777.2:c.1730G>A
NM_002230.4:c.1730G>AMANE SELECT
NM_021991.4:c.1730G>A
NP_001339702.1:p.Arg577His
NP_001339703.1:p.Arg577His
NP_001339704.1:p.Arg577His
NP_001339705.1:p.Arg577His
NP_001339706.1:p.Arg577His
NP_002221.1:p.Arg577His
NP_068831.1:p.Arg577His
LRG_401t2:c.1730G>A
LRG_401:g.33271G>A
NC_000017.10:g.39914694C>T
NM_002230.2:c.1730G>A

Protein change:

R577H

Links:

dbSNP: rs373434456

NCBI 1000 Genomes Browser:

rs373434456

Molecular consequence:

NM_001352773.2:c.1730G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001352774.2:c.1730G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001352775.2:c.1730G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001352776.2:c.1730G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001352777.2:c.1730G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002230.4:c.1730G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_021991.4:c.1730G>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
SCV003857617	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Feb 6, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30847666, 32880476 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003857617

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Feb 6, 2023)

germline

clinical testing

PubMed (2)
[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

Large next-generation sequencing gene panels in genetic heart disease: yield of pathogenic variants and variants of unknown significance.

van Lint FHM, Mook ORF, Alders M, Bikker H, Lekanne Dit Deprez RH, Christiaans I.

Neth Heart J. 2019 Jun;27(6):304-309. doi: 10.1007/s12471-019-1250-5.

PubMed [citation]

PMID:: 30847666
PMCID:: PMC6533346

Implications of Genetic Testing in Dilated Cardiomyopathy.

Verdonschot JAJ, Hazebroek MR, Krapels IPC, Henkens MTHM, Raafs A, Wang P, Merken JJ, Claes GRF, Vanhoutte EK, van den Wijngaard A, Heymans SRB, Brunner HG.

Circ Genom Precis Med. 2020 Oct;13(5):476-487. doi: 10.1161/CIRCGEN.120.003031. Epub 2020 Sep 3.

PubMed [citation]

PMID:: 32880476

Details of each submission

From Ambry Genetics, SCV003857617.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The p.R577H variant (also known as c.1730G>A), located in coding exon 9 of the JUP gene, results from a G to A substitution at nucleotide position 1730. The arginine at codon 577 is replaced by histidine, an amino acid with highly similar properties. This variant co-occurred with variants in other cardiac-related genes in individuals with noncompaction cardiomyopathy and dilated cardiomyopathy (van Lint FHM et al. Neth Heart J, 2019 Jun;27:304-309; Verdonschot JAJ et al. Circ Genom Precis Med, 2020 Oct;13:476-487). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration 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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