NM_002230.4(JUP):c.578T>C (p.Met193Thr) AND multiple conditions

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 7, 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:: RCV000468133.10

Allele description [Variation Report for NM_002230.4(JUP):c.578T>C (p.Met193Thr)]

NM_002230.4(JUP):c.578T>C (p.Met193Thr)

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.578T>C (p.Met193Thr)

HGVS:

NC_000017.11:g.41769098A>G
NG_009090.2:g.22615T>C
NM_001352773.2:c.578T>C
NM_001352774.2:c.578T>C
NM_001352775.2:c.578T>C
NM_001352776.2:c.578T>C
NM_001352777.2:c.578T>C
NM_002230.4:c.578T>CMANE SELECT
NM_021991.4:c.578T>C
NP_001339702.1:p.Met193Thr
NP_001339703.1:p.Met193Thr
NP_001339704.1:p.Met193Thr
NP_001339705.1:p.Met193Thr
NP_001339706.1:p.Met193Thr
NP_002221.1:p.Met193Thr
NP_068831.1:p.Met193Thr
NP_068831.1:p.Met193Thr
LRG_401t2:c.578T>C
LRG_401:g.22615T>C
NC_000017.10:g.39925350A>G
NM_002230.2:c.578T>C
NM_021991.3:c.578T>C
NM_021991.4:c.578T>C

Protein change:

M193T

Links:

dbSNP: rs139496777

NCBI 1000 Genomes Browser:

rs139496777

Molecular consequence:

NM_001352773.2:c.578T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001352774.2:c.578T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001352775.2:c.578T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001352776.2:c.578T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001352777.2:c.578T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002230.4:c.578T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_021991.4:c.578T>C - missense variant - [Sequence Ontology: SO:0001583]

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; Arrhythmogenic right ventricular cardiomyopathy, type 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
SCV000550405	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 7, 2025)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27532257, 31983221, 28492532
SCV002782350	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 12, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000550405

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 7, 2025)

germline

clinical testing

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

SCV002782350

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 12, 2021)

unknown

clinical testing

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

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, Mazzarotto F, Blair E, Seller A, Taylor JC, Minikel EV, Exome Aggregation Consortium, MacArthur DG, Farrall M, Cook SA, Watkins H.

Genet Med. 2017 Feb;19(2):192-203. doi: 10.1038/gim.2016.90. Epub 2016 Aug 17.

PubMed [citation]

PMID:: 27532257
PMCID:: PMC5116235

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

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000550405.9

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

Description

This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 193 of the JUP protein (p.Met193Thr). This variant is present in population databases (rs139496777, gnomAD 0.01%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 27532257, 31983221). ClinVar contains an entry for this variant (Variation ID: 222661). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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, SCV002782350.1

#	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

Last Updated: Mar 11, 2025

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