NM_001943.5(DSG2):c.889G>A (p.Asp297Asn) AND Arrhythmogenic right ventricular cardiomyopathy, type 10

Clinical significance:Uncertain significance (Last evaluated: Jul 30, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000558472.2

Allele description [Variation Report for NM_001943.5(DSG2):c.889G>A (p.Asp297Asn)]

NM_001943.5(DSG2):c.889G>A (p.Asp297Asn)

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.889G>A (p.Asp297Asn)
Other names:
p.D297N:GAT>AAT
HGVS:
  • NC_000018.10:g.31524763G>A
  • NG_007072.3:g.31522G>A
  • NM_001943.5:c.889G>AMANE SELECT
  • NP_001934.2:p.Asp297Asn
  • LRG_397t1:c.889G>A
  • LRG_397:g.31522G>A
  • NC_000018.9:g.29104726G>A
  • NM_001943.3:c.889G>A
  • NM_001943.4:c.889G>A
Protein change:
D297N
Links:
dbSNP: rs751012696
NCBI 1000 Genomes Browser:
rs751012696
Molecular consequence:
  • NM_001943.5:c.889G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Arrhythmogenic right ventricular cardiomyopathy, type 10 (ARVD10)
Synonyms:
ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 10; Arrhythmogenic right ventricular dysplasia type 10; Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy10
Identifiers:
MONDO: MONDO:0012434; MedGen: C1857777; OMIM: 610193

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000641997Invitaecriteria provided, single submitter
Uncertain significance
(Jul 30, 2018)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Desmoglein-2 and desmocollin-2 mutations in dutch arrhythmogenic right ventricular dysplasia/cardiomypathy patients: results from a multicenter study.

Bhuiyan ZA, Jongbloed JD, van der Smagt J, Lombardi PM, Wiesfeld AC, Nelen M, Schouten M, Jongbloed R, Cox MG, van Wolferen M, Rodriguez LM, van Gelder IC, Bikker H, Suurmeijer AJ, van den Berg MP, Mannens MM, Hauer RN, Wilde AA, van Tintelen JP.

Circ Cardiovasc Genet. 2009 Oct;2(5):418-27. doi: 10.1161/CIRCGENETICS.108.839829. Epub 2009 Aug 1.

PubMed [citation]
PMID:
20031616

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, SCV000641997.2

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

Description

This sequence change replaces aspartic acid with asparagine at codon 297 of the DSG2 protein (p.Asp297Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs751012696, ExAC 0.009%). This variant has been reported in two individuals affected with arrhythmogenic right ventriculardysplasia (ARVD) (PMID: 20031616, 20857253). However, in one of these cases it was found in homozygosis and in the other one co-occurring with a pathogenic variant in the PKP2 gene. ClinVar contains an entry for this variant (Variation ID: 199804). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this is a rare missense change that has been found in two ARVD patients.  In the absence of confirmed segregation or functional studies, at this time this change has been classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 8, 2021

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