NM_001943.5(DSG2):c.3040G>A (p.Val1014Ile) AND Arrhythmogenic right ventricular dysplasia 10

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 22, 2024
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:: RCV000473314.9

Allele description [Variation Report for NM_001943.5(DSG2):c.3040G>A (p.Val1014Ile)]

NM_001943.5(DSG2):c.3040G>A (p.Val1014Ile)

Genes:

DSG2-AS1:DSG2 antisense RNA 1 [Gene - HGNC]
DSG2:desmoglein 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_001943.5(DSG2):c.3040G>A (p.Val1014Ile)

Other names:

p.V1014I:GTC>ATC

HGVS:

NC_000018.10:g.31546426G>A
NG_007072.3:g.53185G>A
NM_001943.5:c.3040G>AMANE SELECT
NP_001934.2:p.Val1014Ile
LRG_397t1:c.3040G>A
LRG_397:g.53185G>A
NC_000018.9:g.29126389G>A
NM_001943.3:c.3040G>A
NM_001943.4:c.3040G>A
c.3040G>A

Protein change:

V1014I

Links:

dbSNP: rs200830807

NCBI 1000 Genomes Browser:

rs200830807

Molecular consequence:

NM_001943.5:c.3040G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Arrhythmogenic right ventricular dysplasia 10
Synonyms:: ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 10; Arrhythmogenic right ventricular dysplasia/cardiomyopathy, type 10; Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy10
Identifiers:: MONDO: MONDO:0012434; MedGen: C1857777; OMIM: 610193

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000551018	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 22, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 20716751, 23861362, 24503780, 27532257, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000551018

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 22, 2024)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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

Prevalence of desmosomal protein gene mutations in patients with dilated cardiomyopathy.

Elliott P, O'Mahony C, Syrris P, Evans A, Rivera Sorensen C, Sheppard MN, Carr-White G, Pantazis A, McKenna WJ.

Circ Cardiovasc Genet. 2010 Aug;3(4):314-22. doi: 10.1161/CIRCGENETICS.110.937805.

PubMed [citation]

PMID:: 20716751

Interpreting secondary cardiac disease variants in an exome cohort.

Ng D, Johnston JJ, Teer JK, Singh LN, Peller LC, Wynter JS, Lewis KL, Cooper DN, Stenson PD, Mullikin JC, Biesecker LG; NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program.

Circ Cardiovasc Genet. 2013 Aug;6(4):337-46. doi: 10.1161/CIRCGENETICS.113.000039. Epub 2013 Jul 16.

PubMed [citation]

PMID:: 23861362
PMCID:: PMC3887521

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000551018.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1014 of the DSG2 protein (p.Val1014Ile). This variant is present in population databases (rs200830807, gnomAD 0.01%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 20716751, 23861362, 24503780, 27532257). ClinVar contains an entry for this variant (Variation ID: 44309). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DSG2 protein function with a negative predictive value of 95%. 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

Last Updated: May 16, 2025

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