NM_001943.5(DSG2):c.918G>A (p.Trp306Ter) AND Arrhythmogenic right ventricular dysplasia 10

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Apr 29, 2024
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:: RCV000018304.48

Allele description [Variation Report for NM_001943.5(DSG2):c.918G>A (p.Trp306Ter)]

NM_001943.5(DSG2):c.918G>A (p.Trp306Ter)

Gene:

DSG2:desmoglein 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_001943.5(DSG2):c.918G>A (p.Trp306Ter)

Other names:

W305*; p.W306*:TGG>TGA

HGVS:

NC_000018.10:g.31524792G>A
NG_007072.3:g.31551G>A
NM_001943.5:c.918G>AMANE SELECT
NP_001934.2:p.Trp306Ter
NP_001934.2:p.Trp306Ter
LRG_397t1:c.918G>A
LRG_397:g.31551G>A
LRG_397p1:p.Trp306Ter
NC_000018.9:g.29104755G>A
NG_007072.2:g.31551G>A
NM_001943.3:c.918G>A

Note:

NCBI staff reviewed the sequence information reported in PubMed 16773573 to determine the location of this allele on current reference sequence.

Protein change:

W306*; TRP305TER

Links:

OMIM: 125671.0002; dbSNP: rs121913007

NCBI 1000 Genomes Browser:

rs121913007

Molecular consequence:

NM_001943.5:c.918G>A - nonsense - [Sequence Ontology: SO:0001587]

Observations:

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
SCV000038583	OMIM	no assertion criteria provided	Pathogenic (Jul 1, 2006)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002232679	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 29, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 17105751, 31386562, 16773573, 28492532
SCV002580542	MGZ Medical Genetics Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 28, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004809101	KardioGenetik, Herz- und Diabeteszentrum NRW	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 14, 2024)	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	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Desmoglein-2 mutations in arrhythmogenic right ventricular cardiomyopathy: a genotype-phenotype characterization of familial disease.

Syrris P, Ward D, Asimaki A, Evans A, Sen-Chowdhry S, Hughes SE, McKenna WJ.

Eur Heart J. 2007 Mar;28(5):581-8. Epub 2006 Nov 14.

PubMed [citation]

PMID:: 17105751

Arrhythmogenic Right Ventricular Cardiomyopathy-Associated Desmosomal Variants Are Rarely De Novo.

van Lint FHM, Murray B, Tichnell C, Zwart R, Amat N, Lekanne Deprez RH, Dittmann S, Stallmeyer B, Calkins H, van der Smagt JJ, van den Wijngaard A, Dooijes D, van der Zwaag PA, Schulze-Bahr E, Judge DP, Jongbloed JDH, van Tintelen JP, James CA.

Circ Genom Precis Med. 2019 Aug;12(8):e002467. doi: 10.1161/CIRCGEN.119.002467. Epub 2019 Aug 6.

PubMed [citation]

PMID:: 31386562

See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000038583.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

For discussion of the trp305-to-ter (W305X) mutation in the DSG2 gene that was found in compound heterozygous state in a patient with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD10; 610193) by Awad et al. (2006), see 125671.0001.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002232679.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Trp306*) in the DSG2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DSG2 are known to be pathogenic (PMID: 17105751, 31386562). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with arrhythmogenic right ventricular dysplasia/cardiomyopathy (PMID: 16773573). This variant is also known as W305X. ClinVar contains an entry for this variant (Variation ID: 16811). For these reasons, this variant has been classified as Pathogenic.

#	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 MGZ Medical Genetics Center, SCV002580542.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	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	germline	yes	not provided	not provided	not provided		2	not provided	not provided	not provided

From KardioGenetik, Herz- und Diabeteszentrum NRW, SCV004809101.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	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	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Jun 22, 2025

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