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NM_001943.5(DSG2):c.1781T>C (p.Leu594Pro)

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Interpretation:
Conflicting interpretations of pathogenicity​

Benign(2);Likely benign(5);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
10 (Most recent: Sep 23, 2021)
Last evaluated:
Nov 25, 2020
Accession:
VCV000044287.11
Variation ID:
44287
Description:
single nucleotide variant
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NM_001943.5(DSG2):c.1781T>C (p.Leu594Pro)

Allele ID
53454
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
18q12.1
Genomic location
18: 31538880 (GRCh38) GRCh38 UCSC
18: 29118843 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_397:g.45639T>C
LRG_397t1:c.1781T>C
NC_000018.10:g.31538880T>C
... more HGVS
Protein change
L594P
Other names
-
Canonical SPDI
NC_000018.10:31538879:T:C
Functional consequence
-
Global minor allele frequency (GMAF)
0.00060 (C)

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00022
The Genome Aggregation Database (gnomAD), exomes 0.00063
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00032
Trans-Omics for Precision Medicine (TOPMed) 0.00041
1000 Genomes Project 0.00060
Exome Aggregation Consortium (ExAC) 0.00055
Links
ClinGen: CA021553
dbSNP: rs199681901
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Benign/Likely benign 2 criteria provided, multiple submitters, no conflicts Nov 25, 2020 RCV001085411.3
Likely benign 2 criteria provided, single submitter Jun 24, 2013 RCV000172530.4
Likely benign 1 criteria provided, single submitter Mar 7, 2018 RCV000618191.1
Benign 1 criteria provided, single submitter Aug 14, 2018 RCV000776195.1
Likely benign 1 criteria provided, single submitter Apr 6, 2018 RCV000852742.1
Conflicting interpretations of pathogenicity 3 criteria provided, conflicting interpretations Jan 22, 2018 RCV000037272.4
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
DSG2 Little evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
638 1094

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely benign
(Mar 07, 2018)
criteria provided, single submitter
Method: clinical testing
Cardiovascular phenotype
Allele origin: germline
Ambry Genetics
Accession: SCV000735732.3
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (2)
Comment:
General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance;In silico models in agreement (benign)
Likely benign
(Nov 25, 2020)
criteria provided, single submitter
Method: clinical testing
Arrhythmogenic right ventricular cardiomyopathy, type 10
Allele origin: germline
Invitae
Accession: SCV000561400.6
Submitted: (Jan 07, 2021)
Evidence details
Likely benign
(Jun 24, 2013)
criteria provided, single submitter
Method: research
Not provided
Allele origin: unknown
Biesecker Lab/Clinical Genomics Section,National Institutes of Health
Study: ClinSeq
Accession: SCV000050911.1
Submitted: (Mar 10, 2015)
Comments (2):
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for … (more)
Medical sequencing
Evidence details
Likely benign
(Jan 22, 2018)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
GeneDx
Accession: SCV000714372.1
Submitted: (Mar 26, 2018)
Evidence details
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
Benign
(Aug 14, 2018)
criteria provided, single submitter
Method: clinical testing
Cardiomyopathy
Allele origin: germline
Color Health, Inc
Accession: SCV000911324.1
Submitted: (Nov 06, 2018)
Evidence details
Uncertain significance
(Aug 27, 2014)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000060929.5
Submitted: (Mar 21, 2019)
Evidence details
Publications
PubMed (2)
Comment:
Variant classified as Uncertain Significance - Favor Benign. The Leu594Pro varia nt in DSG2 has been identified in 4/8470 European American chromosomes by the NH … (more)
Likely benign
(Apr 06, 2018)
criteria provided, single submitter
Method: clinical testing
Dilated cardiomyopathy
Allele origin: germline
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego
Accession: SCV000995459.1
Submitted: (Jun 12, 2019)
Evidence details
Benign
(May 11, 2018)
criteria provided, single submitter
Method: clinical testing
Arrhythmogenic right ventricular cardiomyopathy, type 10
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV001286958.1
Submitted: (Feb 20, 2020)
Evidence details
Publications
PubMed (3)
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
Likely benign
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001975715.1
Submitted: (Sep 21, 2021)
Evidence details
Benign
(-)
no assertion criteria provided
Method: clinical testing
not specified
Allele origin: germline
Clinical Genetics,Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001924538.1
Submitted: (Sep 23, 2021)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Genetic Analysis of Arrhythmogenic Diseases in the Era of NGS: The Complexity of Clinical Decision-Making in Brugada Syndrome. Allegue C PloS one 2015 PMID: 26230511
Interpreting secondary cardiac disease variants in an exome cohort. Ng D Circulation. Cardiovascular genetics 2013 PMID: 23861362
Distinguishing arrhythmogenic right ventricular cardiomyopathy/dysplasia-associated mutations from background genetic noise. Kapplinger JD Journal of the American College of Cardiology 2011 PMID: 21636032

Text-mined citations for rs199681901...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 07, 2021