NM_001943.5(DSG2):c.745dup (p.Thr249fs) AND Arrhythmogenic right ventricular dysplasia 10

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 16, 2019
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:: RCV001222719.7

Allele description [Variation Report for NM_001943.5(DSG2):c.745dup (p.Thr249fs)]

NM_001943.5(DSG2):c.745dup (p.Thr249fs)

Gene:

DSG2:desmoglein 2 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_001943.5(DSG2):c.745dup (p.Thr249fs)

HGVS:

NC_000018.10:g.31524502dup
NG_007072.3:g.31261dup
NM_001943.5:c.745dupMANE SELECT
NP_001934.2:p.Thr249fs
LRG_397t1:c.745dup
LRG_397:g.31261dup
NC_000018.9:g.29104464_29104465insA
NC_000018.9:g.29104465dup
NM_001943.3:c.745dup

Protein change:

T249fs

Links:

dbSNP: rs2073148989

NCBI 1000 Genomes Browser:

rs2073148989

Molecular consequence:

NM_001943.5:c.745dup - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV001394835	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 16, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23381804, 23911551, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001394835

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 16, 2019)

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

Mutated desmoglein-2 proteins are incorporated into desmosomes and exhibit dominant-negative effects in arrhythmogenic right ventricular cardiomyopathy.

Rasmussen TB, Palmfeldt J, Nissen PH, Magnoni R, Dalager S, Jensen UB, Kim WY, Heickendorff L, Mølgaard H, Jensen HK, Baandrup UT, Bross P, Mogensen J.

Hum Mutat. 2013 May;34(5):697-705. doi: 10.1002/humu.22289. Epub 2013 Mar 11.

PubMed [citation]

PMID:: 23381804

Mechanistic basis of desmosome-targeted diseases.

Al-Jassar C, Bikker H, Overduin M, Chidgey M.

J Mol Biol. 2013 Nov 1;425(21):4006-22. doi: 10.1016/j.jmb.2013.07.035. Epub 2013 Aug 2. Review.

PubMed [citation]

PMID:: 23911551
PMCID:: PMC3807649

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001394835.6

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

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in DSG2 are known to be pathogenic (PMID: 23381804, 23911551). This variant has not been reported in the literature in individuals with DSG2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Thr249Asnfs*19) in the DSG2 gene. It is expected to result in an absent or disrupted protein product.

#	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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