NM_001943.5(DSG2):c.875G>A (p.Arg292His) AND Cardiomyopathy

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 22, 2023
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:: RCV000770549.6

Allele description [Variation Report for NM_001943.5(DSG2):c.875G>A (p.Arg292His)]

NM_001943.5(DSG2):c.875G>A (p.Arg292His)

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.875G>A (p.Arg292His)

HGVS:

NC_000018.10:g.31524749G>A
NG_007072.3:g.31508G>A
NM_001943.5:c.875G>AMANE SELECT
NP_001934.2:p.Arg292His
LRG_397t1:c.875G>A
LRG_397:g.31508G>A
NC_000018.9:g.29104712G>A
NM_001943.3:c.875G>A
NM_001943.4:c.875G>A
c.875G>A

Protein change:

R292H

Links:

dbSNP: rs185821167

NCBI 1000 Genomes Browser:

rs185821167

Molecular consequence:

NM_001943.5:c.875G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000901996	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario - Canadian Open Genetics Repository	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 21, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001735670	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 22, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25172079, 31702781, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000901996

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario - Canadian Open Genetics Repository

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 21, 2022)

germline

clinical testing

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

SCV001735670

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 22, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A recessive inheritance pattern contributes to arrhythmogenic biventricular cardiomyopathy.

Jiménez-Jáimez J, López Moreno E, Barrio López MT, González-Molina M, Alvarez M, Tercedor L.

Rev Esp Cardiol (Engl Ed). 2014 Sep;67(9):772-4. doi: 10.1016/j.rec.2014.04.012. Epub 2014 Jul 10. No abstract available.

PubMed [citation]

PMID:: 25172079

Myocardial fibrosis in arrhythmogenic cardiomyopathy: a genotype-phenotype correlation study.

Segura-Rodríguez D, Bermúdez-Jiménez FJ, Carriel V, López-Fernández S, González-Molina M, Oyonarte Ramírez JM, Fernández-Navarro L, García-Roa MD, Cabrerizo EM, Durand-Herrera D, Alaminos M, Campos A, Macías R, Álvarez M, Tercedor L, Jiménez-Jáimez J.

Eur Heart J Cardiovasc Imaging. 2020 Apr 1;21(4):378-386. doi: 10.1093/ehjci/jez277.

PubMed [citation]

PMID:: 31702781

See all PubMed Citations (3)

Details of each submission

From CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario - Canadian Open Genetics Repository, SCV000901996.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Color Diagnostics, LLC DBA Color Health, SCV001735670.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This missense variant replaces arginine with histidine at codon 292 of the DSG2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in the homozygous state in several individuals affected with arrhythmogenic right ventricular cardiomyopathy/dysplasia and in the heterozygous state in their unaffected relatives (PMID: 25172079, 31702781). This variant has also been identified in 24/280756 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 7, 2024

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