NM_002230.4(JUP):c.1355C>T (p.Thr452Met) AND multiple conditions

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 31, 2022
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:: RCV000819254.7

Allele description [Variation Report for NM_002230.4(JUP):c.1355C>T (p.Thr452Met)]

NM_002230.4(JUP):c.1355C>T (p.Thr452Met)

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.1355C>T (p.Thr452Met)

Other names:

p.T452M:ACG>ATG

HGVS:

NC_000017.11:g.41763125G>A
NG_009090.2:g.28588C>T
NM_001352773.2:c.1355C>T
NM_001352774.2:c.1355C>T
NM_001352775.2:c.1355C>T
NM_001352776.2:c.1355C>T
NM_001352777.2:c.1355C>T
NM_002230.4:c.1355C>TMANE SELECT
NM_021991.4:c.1355C>T
NP_001339702.1:p.Thr452Met
NP_001339703.1:p.Thr452Met
NP_001339704.1:p.Thr452Met
NP_001339705.1:p.Thr452Met
NP_001339706.1:p.Thr452Met
NP_002221.1:p.Thr452Met
NP_068831.1:p.Thr452Met
LRG_401t2:c.1355C>T
LRG_401:g.28588C>T
NC_000017.10:g.39919377G>A
NM_002230.2:c.1355C>T

Protein change:

T452M

Links:

dbSNP: rs781888888

NCBI 1000 Genomes Browser:

rs781888888

Molecular consequence:

NM_001352773.2:c.1355C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001352774.2:c.1355C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001352775.2:c.1355C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001352776.2:c.1355C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001352777.2:c.1355C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002230.4:c.1355C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_021991.4:c.1355C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Naxos disease (NXD)
Synonyms:: KERATOSIS PALMOPLANTARIS WITH ARRHYTHMOGENIC CARDIOMYOPATHY; PALMOPLANTAR KERATODERMA WITH ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY AND WOOLLY HAIR; WOOLLY HAIR, PALMOPLANTAR KERATODERMA, AND CARDIAC ABNORMALITIES; 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
SCV000959904	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 31, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30453078, 28492532
SCV002789183	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 9, 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

SCV000959904

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 31, 2022)

germline

clinical testing

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

SCV002789183

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 9, 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

A targeted next-generation gene panel reveals a novel heterozygous nonsense variant in the TP63 gene in patients with arrhythmogenic cardiomyopathy.

Poloni G, Calore M, Rigato I, Marras E, Minervini G, Mazzotti E, Lorenzon A, Li Mura IEA, Telatin A, Zara I, Simionati B, Perazzolo Marra M, Ponti J, Occhi G, Vitiello L, Daliento L, Thiene G, Basso C, Corrado D, Tosatto S, Bauce B, Rampazzo A, et al.

Heart Rhythm. 2019 May;16(5):773-780. doi: 10.1016/j.hrthm.2018.11.015. Epub 2018 Nov 17.

PubMed [citation]

PMID:: 30453078

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000959904.4

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 201824). This missense change has been observed in individual(s) with arrhythmogenic cardiomyopathy (PMID: 30453078). This variant is present in population databases (rs781888888, gnomAD 0.01%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 452 of the JUP protein (p.Thr452Met).

#	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, SCV002789183.1

#	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 5, 2024

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