NM_002230.4(JUP):c.1787C>T (p.Ser596Leu) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 16, 2021
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:: RCV002397399.2

Allele description [Variation Report for NM_002230.4(JUP):c.1787C>T (p.Ser596Leu)]

NM_002230.4(JUP):c.1787C>T (p.Ser596Leu)

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.1787C>T (p.Ser596Leu)

HGVS:

NC_000017.11:g.41757771G>A
NG_009090.2:g.33942C>T
NM_001352773.2:c.1787C>T
NM_001352774.2:c.1787C>T
NM_001352775.2:c.1787C>T
NM_001352776.2:c.1787C>T
NM_001352777.2:c.1787C>T
NM_002230.4:c.1787C>TMANE SELECT
NM_021991.4:c.1787C>T
NP_001339702.1:p.Ser596Leu
NP_001339703.1:p.Ser596Leu
NP_001339704.1:p.Ser596Leu
NP_001339705.1:p.Ser596Leu
NP_001339706.1:p.Ser596Leu
NP_002221.1:p.Ser596Leu
NP_068831.1:p.Ser596Leu
LRG_401t2:c.1787C>T
LRG_401:g.33942C>T
NC_000017.10:g.39914023G>A
NM_002230.2:c.1787C>T

Protein change:

S596L

Links:

dbSNP: rs940226194

NCBI 1000 Genomes Browser:

rs940226194

Molecular consequence:

NM_001352773.2:c.1787C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001352774.2:c.1787C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001352775.2:c.1787C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001352776.2:c.1787C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001352777.2:c.1787C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002230.4:c.1787C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_021991.4:c.1787C>T - 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
SCV002714407	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Apr 16, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002714407

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Apr 16, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Reevaluating the Genetic Contribution of Monogenic Dilated Cardiomyopathy.

Mazzarotto F, Tayal U, Buchan RJ, Midwinter W, Wilk A, Whiffin N, Govind R, Mazaika E, de Marvao A, Dawes TJW, Felkin LE, Ahmad M, Theotokis PI, Edwards E, Ing AY, Thomson KL, Chan LLH, Sim D, Baksi AJ, Pantazis A, Roberts AM, Watkins H, et al.

Circulation. 2020 Feb 4;141(5):387-398. doi: 10.1161/CIRCULATIONAHA.119.037661. Epub 2020 Jan 27.

PubMed [citation]

PMID:: 31983221
PMCID:: PMC7004454

Details of each submission

From Ambry Genetics, SCV002714407.2

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

Description

The p.S596L variant (also known as c.1787C>T), located in coding exon 10 of the JUP gene, results from a C to T substitution at nucleotide position 1787. The serine at codon 596 is replaced by leucine, an amino acid with dissimilar properties. This variant was reported in one individual from a dilated cardiomyopathy (DCM) cohort with limited clinical details provided (Mazzarotto F et al. Circulation, 2020 02;141:387-398). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated 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: May 16, 2025

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