U.S. flag

An official website of the United States government

NM_001943.5(DSG2):c.445G>A (p.Val149Ile) AND Arrhythmogenic right ventricular cardiomyopathy

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
May 14, 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:
RCV000202938.4

Allele description [Variation Report for NM_001943.5(DSG2):c.445G>A (p.Val149Ile)]

NM_001943.5(DSG2):c.445G>A (p.Val149Ile)

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.445G>A (p.Val149Ile)
HGVS:
  • NC_000018.10:g.31521165G>A
  • NG_007072.3:g.27924G>A
  • NM_001943.5:c.445G>AMANE SELECT
  • NP_001934.2:p.Val149Ile
  • LRG_397t1:c.445G>A
  • LRG_397:g.27924G>A
  • NC_000018.9:g.29101128G>A
  • NM_001943.3:c.445G>A
  • NM_001943.4:c.445G>A
Protein change:
V149I
Links:
dbSNP: rs372606274
NCBI 1000 Genomes Browser:
rs372606274
Molecular consequence:
  • NM_001943.5:c.445G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
7

Condition(s)

Name:
Arrhythmogenic right ventricular cardiomyopathy (ARVD)
Synonyms:
Cardiomyopathy, ARVC; Arrhythmogenic right ventricular dysplasia
Identifiers:
MONDO: MONDO:0016587; MeSH: D019571; MedGen: C0349788

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000257910Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
criteria provided, single submitter

(DGD Variant Analysis Guidelines)		Uncertain significance
(May 14, 2015) 		unknownclinical testing

DGD_Variant_Analysis_Guidelines.docx,

Citation Link,

SCV004819442All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(May 14, 2024) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown7not providednot provided143475not providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Truncating plakophilin-2 mutations in arrhythmogenic cardiomyopathy are associated with protein haploinsufficiency in both myocardium and epidermis.

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

Circ Cardiovasc Genet. 2014 Jun;7(3):230-40. doi: 10.1161/CIRCGENETICS.113.000338. Epub 2014 Apr 4.

PubMed [citation]
PMID:
24704780

Implications of Genetic Testing in Dilated Cardiomyopathy.

Verdonschot JAJ, Hazebroek MR, Krapels IPC, Henkens MTHM, Raafs A, Wang P, Merken JJ, Claes GRF, Vanhoutte EK, van den Wijngaard A, Heymans SRB, Brunner HG.

Circ Genom Precis Med. 2020 Oct;13(5):476-487. doi: 10.1161/CIRCGEN.120.003031. Epub 2020 Sep 3.

PubMed [citation]
PMID:
32880476
See all PubMed Citations (4)

Details of each submission

From Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia, SCV000257910.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From All of Us Research Program, National Institutes of Health, SCV004819442.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided7not providednot providedclinical testing PubMed (4)

Description

This missense variant replaces valine with isoleucine at codon 149 of the DSG2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in two individuals affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 24704780, 34012299) and in one individual affected with dilated cardiomyopathy (PMID: 32880476). This variant has been identified in 8/280720 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown143475not providednot provided7not providednot providednot provided

Last Updated: Jan 13, 2025