NM_002230.4(JUP):c.1512G>T (p.Leu504Phe) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 2, 2023
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:: RCV003793315.2

Allele description [Variation Report for NM_002230.4(JUP):c.1512G>T (p.Leu504Phe)]

NM_002230.4(JUP):c.1512G>T (p.Leu504Phe)

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.1512G>T (p.Leu504Phe)

HGVS:

NC_000017.11:g.41758856C>A
NG_009090.2:g.32857G>T
NM_001352773.2:c.1512G>T
NM_001352774.2:c.1512G>T
NM_001352775.2:c.1512G>T
NM_001352776.2:c.1512G>T
NM_001352777.2:c.1512G>T
NM_002230.4:c.1512G>TMANE SELECT
NM_021991.4:c.1512G>T
NP_001339702.1:p.Leu504Phe
NP_001339703.1:p.Leu504Phe
NP_001339704.1:p.Leu504Phe
NP_001339705.1:p.Leu504Phe
NP_001339706.1:p.Leu504Phe
NP_002221.1:p.Leu504Phe
NP_002221.1:p.Leu504Phe
NP_068831.1:p.Leu504Phe
NP_068831.1:p.Leu504Phe
LRG_401t1:c.1512G>T
LRG_401t2:c.1512G>T
LRG_401:g.32857G>T
LRG_401p1:p.Leu504Phe
LRG_401p2:p.Leu504Phe
NC_000017.10:g.39915108C>A
NM_002230.2:c.1512G>T
NM_021991.2:c.1512G>T

Protein change:

L504F

Molecular consequence:

NM_001352773.2:c.1512G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001352774.2:c.1512G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001352775.2:c.1512G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001352776.2:c.1512G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001352777.2:c.1512G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002230.4:c.1512G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_021991.4:c.1512G>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
SCV004580852	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 2, 2023)	germline	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

SCV004580852

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 2, 2023)

germline

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

Citations

PubMed

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

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004580852.1

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

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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with JUP-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 504 of the JUP protein (p.Leu504Phe).

#	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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