NM_001943.5(DSG2):c.3140C>G (p.Thr1047Arg) AND Arrhythmogenic right ventricular dysplasia 10

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 9, 2022
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:: RCV002513475.2

Allele description [Variation Report for NM_001943.5(DSG2):c.3140C>G (p.Thr1047Arg)]

NM_001943.5(DSG2):c.3140C>G (p.Thr1047Arg)

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.3140C>G (p.Thr1047Arg)

HGVS:

NC_000018.10:g.31546526C>G
NG_007072.3:g.53285C>G
NM_001943.5:c.3140C>GMANE SELECT
NP_001934.2:p.Thr1047Arg
LRG_397t1:c.3140C>G
LRG_397:g.53285C>G
NC_000018.9:g.29126489C>G
NM_001943.3:c.3140C>G
c.3140C>G

Protein change:

T1047R

Links:

dbSNP: rs397516707

NCBI 1000 Genomes Browser:

rs397516707

Molecular consequence:

NM_001943.5:c.3140C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Arrhythmogenic right ventricular dysplasia 10
Synonyms:: ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 10; Arrhythmogenic right ventricular cardiomyopathy, type 10; Arrhythmogenic right ventricular dysplasia/cardiomyopathy, type 10; See all synonyms [MedGen]
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
SCV003443784	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 9, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23128240, 20857253, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003443784

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 9, 2022)

germline

clinical testing

PubMed (3)
[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

The C-terminal unique region of desmoglein 2 inhibits its internalization via tail-tail interactions.

Chen J, Nekrasova OE, Patel DM, Klessner JL, Godsel LM, Koetsier JL, Amargo EV, Desai BV, Green KJ.

J Cell Biol. 2012 Nov 12;199(4):699-711. doi: 10.1083/jcb.201202105. Epub 2012 Nov 5.

PubMed [citation]

PMID:: 23128240
PMCID:: PMC3494854

Shared desmosome gene findings in early and late onset arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Tan BY, Jain R, den Haan AD, Chen Y, Dalal D, Tandri H, Amat-Alarcon N, Daly A, Tichnell C, James C, Calkins H, Judge DP.

J Cardiovasc Transl Res. 2010 Dec;3(6):663-73. doi: 10.1007/s12265-010-9224-4. Epub 2010 Sep 21.

PubMed [citation]

PMID:: 20857253
PMCID:: PMC3138067

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV003443784.2

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

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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on DSG2 function (PMID: 23128240). 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"). ClinVar contains an entry for this variant (Variation ID: 44311). This missense change has been observed in individual(s) with DSG2-related conditions (PMID: 20857253). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 1047 of the DSG2 protein (p.Thr1047Arg).

#	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: Feb 14, 2024

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