Submissions for variant NM_001943.5(DSG2):c.1303G>A (p.Asp435Asn)

gnomAD frequency: 0.00003  dbSNP: rs370509593

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000171901	SCV000054848	uncertain significance	not provided	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000155790	SCV000205501	likely benign	not specified	2015-06-04	criteria provided, single submitter	clinical testing	p.Asp435Asn in exon 10 of DSG2: This variant is not expected to have clinical si gnificance because it has been identified in 0.7% (101/14182) of South Asian chr omosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs370509593).
GeneDx	RCV000171901	SCV000233496	benign	not provided	2019-03-28	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 21606396)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001087023	SCV000641962	benign	Arrhythmogenic right ventricular dysplasia 10	2024-01-31	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000770551	SCV000901999	benign	Cardiomyopathy	2020-09-10	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001087023	SCV001284601	likely benign	Arrhythmogenic right ventricular dysplasia 10	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Color Diagnostics, LLC DBA Color Health	RCV000770551	SCV001357600	benign	Cardiomyopathy	2018-11-11	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002381497	SCV002693720	benign	Cardiovascular phenotype	2022-06-10	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Stanford Center for Inherited Cardiovascular Disease, Stanford University	RCV000171901	SCV000280081	likely benign	not provided	2017-07-25	no assertion criteria provided	provider interpretation	Reclassified by our group an testing lab from VUS to Likely Benign based on 0.7% MAF in South Asians in gnomAD. It is present in 205 individuals in that database (195 of them with South Asian ancestry), including 4 homozygotes.
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000171901	SCV001954260	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000171901	SCV001976148	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004754320	SCV005367321	likely benign	DSG2-related disorder	2024-07-29	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).