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NM_001943.5(DSG2):c.430G>A (p.Glu144Lys) AND Arrhythmogenic right ventricular dysplasia 10

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 31, 2023
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:
RCV000810288.5

Allele description [Variation Report for NM_001943.5(DSG2):c.430G>A (p.Glu144Lys)]

NM_001943.5(DSG2):c.430G>A (p.Glu144Lys)

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.430G>A (p.Glu144Lys)
Other names:
p.E144K:GAG>AAG
HGVS:
  • NC_000018.10:g.31521150G>A
  • NG_007072.3:g.27909G>A
  • NM_001943.5:c.430G>AMANE SELECT
  • NP_001934.2:p.Glu144Lys
  • LRG_397t1:c.430G>A
  • LRG_397:g.27909G>A
  • NC_000018.9:g.29101113G>A
  • NM_001943.3:c.430G>A
  • NM_001943.4:c.430G>A
Protein change:
E144K
Links:
dbSNP: rs199842209
NCBI 1000 Genomes Browser:
rs199842209
Molecular consequence:
  • NM_001943.5:c.430G>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 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000950481Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Dec 31, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

PKP2 and DSG2 genetic variations in Latvian arrhythmogenic right ventricular dysplasia/cardiomyopathy registry patients.

Bidina L, Kupics K, Sokolova E, Pavlovics M, Dobele Z, Caunite L, Kalejs O, Gailite L.

Anatol J Cardiol. 2018 Nov;20(5):296-302. doi: 10.14744/AnatolJCardiol.2018.35984.

PubMed [citation]
PMID:
30391969
PMCID:
PMC6280287

Variant panorama in 1,385 index patients and sensitivity of expanded next-generation sequencing panels in arrhythmogenic disorders.

Marschall C, Moscu-Gregor A, Klein HG.

Cardiovasc Diagn Ther. 2019 Oct;9(Suppl 2):S292-S298. doi: 10.21037/cdt.2019.06.06.

PubMed [citation]
PMID:
31737537
PMCID:
PMC6837920
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000950481.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 144 of the DSG2 protein (p.Glu144Lys). This variant is present in population databases (rs199842209, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of arrhythmogenic right ventricular cardiomyopathy (PMID: 30391969, 31737537). ClinVar contains an entry for this variant (Variation ID: 191626). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024