NM_002230.4(JUP):c.1729C>T (p.Arg577Cys) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 21, 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:: RCV001532951.1

Allele description [Variation Report for NM_002230.4(JUP):c.1729C>T (p.Arg577Cys)]

NM_002230.4(JUP):c.1729C>T (p.Arg577Cys)

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.1729C>T (p.Arg577Cys)

HGVS:

NC_000017.11:g.41758443G>A
NG_009090.2:g.33270C>T
NM_001352773.2:c.1729C>T
NM_001352774.2:c.1729C>T
NM_001352775.2:c.1729C>T
NM_001352776.2:c.1729C>T
NM_001352777.2:c.1729C>T
NM_002230.4:c.1729C>TMANE SELECT
NM_021991.4:c.1729C>T
NP_001339702.1:p.Arg577Cys
NP_001339703.1:p.Arg577Cys
NP_001339704.1:p.Arg577Cys
NP_001339705.1:p.Arg577Cys
NP_001339706.1:p.Arg577Cys
NP_002221.1:p.Arg577Cys
NP_068831.1:p.Arg577Cys
LRG_401t1:c.1729C>T
LRG_401t2:c.1729C>T
LRG_401:g.33270C>T
NC_000017.10:g.39914695G>A
NM_002230.2:c.1729C>T
NM_021991.2:c.1729C>T

Protein change:

R577C

Links:

dbSNP: rs782354654

NCBI 1000 Genomes Browser:

rs782354654

Molecular consequence:

NM_001352773.2:c.1729C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001352774.2:c.1729C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001352775.2:c.1729C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001352776.2:c.1729C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001352777.2:c.1729C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002230.4:c.1729C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_021991.4:c.1729C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

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caspase recruitment domain-containing protein 14 isoform X6 [Homo sapiens]
caspase recruitment domain-containing protein 14 isoform X6 [Homo sapiens]
gi|2462498957|ref|XP_054189187.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001748767	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Jun 21, 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

SCV001748767

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Jun 21, 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

Whole-Exome Sequencing Identified a De Novo Mutation of Junction Plakoglobin (p.R577C) in a Chinese Patient with Arrhythmogenic Right Ventricular Cardiomyopathy.

Liu L, Chen C, Li Y, Yu R.

Biomed Res Int. 2019;2019:9103860. doi: 10.1155/2019/9103860.

PubMed [citation]

PMID:: 31275992
PMCID:: PMC6558630

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001748767.1

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

Description

Variant summary: JUP c.1729C>T (p.Arg577Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.6e-05 in 251314 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1729C>T has been reported in the literature as a de novo variant in a patient affected with Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (Liu_2019). This same report shows experimental evidence of decreased experssion of DSG2 and Connexin 43 in mutated cells via Western blot analysis. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS - possibly pathogenic.

#	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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