NM_001943.5(DSG2):c.2434G>T (p.Gly812Cys) AND Cardiomyopathy

Clinical significance:Uncertain significance (Last evaluated: Mar 25, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001183802.1

Allele description [Variation Report for NM_001943.5(DSG2):c.2434G>T (p.Gly812Cys)]

NM_001943.5(DSG2):c.2434G>T (p.Gly812Cys)

Genes:
DSG2-AS1:DSG2 antisense RNA 1 [Gene - HGNC]
DSG2:desmoglein 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
18q12.1
Genomic location:
Preferred name:
NM_001943.5(DSG2):c.2434G>T (p.Gly812Cys)
HGVS:
  • NC_000018.10:g.31545820G>T
  • NG_007072.3:g.52579G>T
  • NM_001943.5:c.2434G>TMANE SELECT
  • NP_001934.2:p.Gly812Cys
  • LRG_397t1:c.2434G>T
  • LRG_397:g.52579G>T
  • LRG_397p1:p.Gly812Ser
  • NC_000018.9:g.29125783G>T
  • NG_007072.2:g.52579G>T
  • NM_001943.3:c.2434G>T
  • NM_001943.4:c.2434G>T
  • NP_001934.2:p.Gly812Ser
  • NR_045216.1:n.1432C>A
  • Q14126:p.Gly812Cys
  • c.2434G>T
Note:
NCBI staff reviewed the sequence information reported in PubMed 16773573 to determine the location of this allele on current reference sequence.
Protein change:
G812C
Links:
UniProtKB: Q14126#VAR_029368; OMIM: 125671.0005; dbSNP: rs121913010
NCBI 1000 Genomes Browser:
rs121913010
Molecular consequence:
  • NM_001943.5:c.2434G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_045216.1:n.1432C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Cardiomyopathy (CMYO)
Identifiers:
MONDO: MONDO:0004994; MedGen: C0878544; Human Phenotype Ontology: HP:0001638

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001349629Color Health, Inccriteria provided, single submitter
Uncertain significance
(Mar 25, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Description

This missense variant replaces glycine with cysteine at codon 812 of the DSG2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. A functional study has shown that this variant does not affect membrane expression of the mutant protein and does not affect cardiomyocyte cohesion in vitro (PMID: 25213555). This variant has been reported in two individuals affected with arrhythmogenic right ventricular cardiomyopathy (ARVC) (PMID: 16773573, 20031617), in an individual affected with probable ARVC (PMID: 20857253) and in an individual affected with exercise-induced ARVC (PMID: 23871885). This variant has been identified in 3/249442 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.

SCV001349629

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Color Health, Inc, SCV001349629.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2021

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