NM_001943.5(DSG2):c.581C>T (p.Ser194Leu) AND Arrhythmogenic right ventricular cardiomyopathy, type 10

Clinical significance:Uncertain significance (Last evaluated: Dec 4, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000642313.1

Allele description [Variation Report for NM_001943.5(DSG2):c.581C>T (p.Ser194Leu)]

NM_001943.5(DSG2):c.581C>T (p.Ser194Leu)

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.581C>T (p.Ser194Leu)
HGVS:
  • NC_000018.10:g.31522140C>T
  • NG_007072.3:g.28899C>T
  • NM_001943.5:c.581C>TMANE SELECT
  • NP_001934.2:p.Ser194Leu
  • LRG_397t1:c.581C>T
  • LRG_397:g.28899C>T
  • NC_000018.9:g.29102103C>T
  • NM_001943.3:c.581C>T
  • c.581C>T
Protein change:
S194L
Links:
dbSNP: rs374875442
NCBI 1000 Genomes Browser:
rs374875442
Molecular consequence:
  • NM_001943.5:c.581C>T - 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
SCV000763982Invitaecriteria provided, single submitter
Uncertain significance
(Dec 4, 2017)
germlineclinical testing

PubMed (2)
[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

Compound and digenic heterozygosity in desmosome genes as a cause of arrhythmogenic right ventricular cardiomyopathy in Japanese patients.

Nakajima T, Kaneko Y, Irie T, Takahashi R, Kato T, Iijima T, Iso T, Kurabayashi M.

Circ J. 2012;76(3):737-43. Epub 2011 Dec 28.

PubMed [citation]
PMID:
22214898

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000763982.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces serine with leucine at codon 194 of the DSG2 protein (p.Ser194Leu). The serine residue is moderately conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs374875442, ExAC 0.02%). This variant has been observed on the opposite chromosome (in trans) from a rare missense variant in an individual affected with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) (PMID 22214898). ClinVar contains an entry for this variant (Variation ID: 44324). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 23, 2021

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