NM_002230.4(JUP):c.389TCA[1] (p.Ile131del) AND multiple conditions

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Jan 28, 2025
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000645204.9

Allele description [Variation Report for NM_002230.4(JUP):c.389TCA[1] (p.Ile131del)]

NM_002230.4(JUP):c.389TCA[1] (p.Ile131del)

Gene:

JUP:junction plakoglobin [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

17q21.2

Genomic location:

Preferred name:

NM_002230.4(JUP):c.389TCA[1] (p.Ile131del)

HGVS:

NC_000017.10:g.39925744_39925746del
NC_000017.11:g.41769492TGA[1]
NG_009090.2:g.22216TCA[1]
NM_001352773.2:c.389TCA[1]
NM_001352774.2:c.389TCA[1]
NM_001352775.2:c.389TCA[1]
NM_001352776.2:c.389TCA[1]
NM_001352777.2:c.389TCA[1]
NM_002230.4:c.389TCA[1]MANE SELECT
NM_021991.4:c.389TCA[1]
NP_001339702.1:p.Ile131del
NP_001339703.1:p.Ile131del
NP_001339704.1:p.Ile131del
NP_001339705.1:p.Ile131del
NP_001339706.1:p.Ile131del
NP_002221.1:p.Ile131del
NP_068831.1:p.Ile131del
LRG_401t1:c.392_394del
LRG_401t2:c.392_394del
LRG_401:g.22216TCA[1]
NC_000017.10:g.39925744TGA[1]
NC_000017.10:g.39925744_39925746del
NC_000017.10:g.39925744_39925746delTGA
NM_002230.2:c.392_394delTCA
NM_002230.4:c.392_394delMANE SELECT
NM_021991.2:c.392_394delTCA

Protein change:

I131del

Links:

dbSNP: rs781818082

NCBI 1000 Genomes Browser:

rs781818082

Molecular consequence:

NM_001352773.2:c.389TCA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001352774.2:c.389TCA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001352775.2:c.389TCA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001352776.2:c.389TCA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001352777.2:c.389TCA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_002230.4:c.389TCA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_021991.4:c.389TCA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

Observations:

Condition(s)

Name:: Naxos disease (NXD)
Synonyms:: KERATOSIS PALMOPLANTARIS WITH ARRHYTHMOGENIC CARDIOMYOPATHY; MAL DE NAXOS; PALMOPLANTAR KERATODERMA WITH ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY AND WOOLLY HAIR; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011017; MedGen: C1832600; Orphanet: 34217; OMIM: 601214

Name:: Arrhythmogenic right ventricular dysplasia 12
Synonyms:: ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 12
Identifiers:: MONDO: MONDO:0012684; MedGen: C1969081; OMIM: 611528

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000766946	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 28, 2025)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20152563, 28492532
SCV002782466	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 29, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003925263	New York Genome Center	criteria provided, single submitter (NYGC Assertion Criteria 2020)	Uncertain significance (Sep 12, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000766946

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 28, 2025)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV002782466

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 29, 2021)

unknown

clinical testing

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

SCV003925263

New York Genome Center

criteria provided, single submitter

(NYGC Assertion Criteria 2020)

Uncertain significance
(Sep 12, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	1	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Compound and digenic heterozygosity contributes to arrhythmogenic right ventricular cardiomyopathy.

Xu T, Yang Z, Vatta M, Rampazzo A, Beffagna G, Pilichou K, Scherer SE, Saffitz J, Kravitz J, Zareba W, Danieli GA, Lorenzon A, Nava A, Bauce B, Thiene G, Basso C, Calkins H, Gear K, Marcus F, Towbin JA; Multidisciplinary Study of Right Ventricular Dysplasia Investigators.

J Am Coll Cardiol. 2010 Feb 9;55(6):587-97. doi: 10.1016/j.jacc.2009.11.020. Erratum in: J Am Coll Cardiol. 2010 Mar 30;55(13):1401. Pillichou, Kalliopi [corrected to Pilichou, Kalliopi].

PubMed [citation]

PMID:: 20152563
PMCID:: PMC2852685

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000766946.5

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

Description

This variant, c.392_394del, results in the deletion of 1 amino acid(s) of the JUP protein (p.Ile131del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs781818082, gnomAD 0.0009%). This variant has been observed in individual(s) with arrhythmogenic right ventricular cardiomyopathy (PMID: 20152563). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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

From Fulgent Genetics, Fulgent Genetics, SCV002782466.1

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

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

From New York Genome Center, SCV003925263.2

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

Description

The c.392_394del variant identified in the JUP gene is predicted to result in deletion of one amino acid [p.(Ile131del)] without causing a shift in the reading frame (in-frame deletion). This variant is observed in 12 individuals across population databases (gnomAD v2.1.1 and v3.1.2, TOPMed Freeze 8) suggesting it is not a common benign variant in the populations represented in those databases. This variant has been identified in one individual affected with arrhythmogenic right ventricular cardiomyopathy [PMID: 20152563], and has also been reported four times in ClinVar as a Variant of Uncertain Significance (ClinVarID:402991). In silico predictions are not available for this variant. Based on the available evidence, the c.392_394del p.(Ile131del) variant identified in the JUP gene is reported as a Variant of Uncertain Significance.

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

Last Updated: May 16, 2025

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