Submissions for variant NM_024422.6(DSC2):c.270G>A (p.Glu90=)

gnomAD frequency: 0.00056  dbSNP: rs138643506

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039430	SCV000063114	likely benign	not specified	2016-07-18	criteria provided, single submitter	clinical testing	p.Glu90Glu in exon 3 of DSC2: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 0.1% (46/66562) of E uropean chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broa dinstitute.org; dbSNP rs138643506).
GeneDx	RCV000039430	SCV000168226	benign	not specified	2014-05-06	criteria provided, single submitter	clinical testing	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 a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000231166	SCV000290735	likely benign	Arrhythmogenic right ventricular dysplasia 11	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000250066	SCV000319071	likely benign	Cardiovascular phenotype	2017-02-09	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
Illumina Laboratory Services, Illumina	RCV000231166	SCV000408106	uncertain significance	Arrhythmogenic right ventricular dysplasia 11	2018-01-13	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000231166	SCV000743500	likely benign	Arrhythmogenic right ventricular dysplasia 11	2017-07-28	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000231166	SCV000744772	likely benign	Arrhythmogenic right ventricular dysplasia 11	2015-09-21	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000777785	SCV000913760	likely benign	Cardiomyopathy	2018-10-15	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000858514	SCV001151506	likely benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	DSC2: BP4, BP7
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000039430	SCV002015143	benign	not specified	2021-10-30	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000777785	SCV002043573	likely benign	Cardiomyopathy	2023-05-16	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000231166	SCV000733782	likely benign	Arrhythmogenic right ventricular dysplasia 11		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000039430	SCV001923652	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000858514	SCV001957261	likely benign	not provided		no assertion criteria provided	clinical testing