Submissions for variant NM_004415.4(DSP):c.4609C>T (p.Arg1537Cys)

gnomAD frequency: 0.00925  dbSNP: rs28763967

Total submissions: 21

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000038052	SCV000051537	benign	not specified	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038052	SCV000061718	benign	not specified	2010-09-21	criteria provided, single submitter	clinical testing	Arg1537Cys in exon 23 of DSP: This missense variant has been reported in the SN P database with a frequency of 5.6% (dbSNP; rs28763967). While we cannot exclude the possibility that this variant contributes to disease, its high frequency su ggests that it is more likely benign.
Invitae	RCV001080033	SCV000288540	benign	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000038052	SCV000310362	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000331603	SCV000465062	likely benign	Arrhythmogenic right ventricular dysplasia 8	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.
Illumina Laboratory Services, Illumina	RCV000388441	SCV000465063	benign	Woolly hair-skin fragility syndrome	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000296538	SCV000465064	benign	Lethal acantholytic epidermolysis bullosa	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000434359	SCV000511209	likely benign	not provided	2017-01-03	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
Agnes Ginges Centre for Molecular Cardiology, Centenary Institute	RCV000584761	SCV000692515	benign	Arrhythmogenic right ventricular cardiomyopathy; Sudden unexplained death	2017-03-15	criteria provided, single submitter	research	The DSP Arg1537Cys variant has a high frequency in the 1000 genomes project (MAF= 0.0036; http://www.1000genomes.org/), as well as the Exome Aggregation Consortium dataset (MAF= 0.0091; http://exac.broadinstitute.org/). Furthermore, although his variant was identified in a sudden death patient with ARVC/D on postmortem it did not segregate with disease in an affected ARVC family member. As a result we classify the DSP Arg1537Cys variant as "benign".
Ambry Genetics	RCV000621921	SCV000734887	benign	Cardiovascular phenotype	2015-10-09	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000434359	SCV000883749	benign	not provided	2023-11-27	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000776035	SCV000910630	benign	Cardiomyopathy	2018-03-08	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852996	SCV000995747	benign	Arrhythmogenic right ventricular cardiomyopathy; Brugada syndrome	2019-02-16	criteria provided, single submitter	clinical testing
GeneDx	RCV000434359	SCV001843437	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 33232181, 31402444, 27153395, 19863551, 25445213)
CeGaT Center for Human Genetics Tuebingen	RCV000434359	SCV002497384	likely benign	not provided	2024-05-01	criteria provided, single submitter	clinical testing	DSP: PM5, BS1, BS2
Fulgent Genetics, Fulgent Genetics	RCV002490517	SCV002800372	benign	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8; Lethal acantholytic epidermolysis bullosa; Woolly hair-skin fragility syndrome; Keratosis palmoplantaris striata 2; Cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis	2021-08-09	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000434359	SCV001743214	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000038052	SCV001922853	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000038052	SCV001931519	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000038052	SCV001953075	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000038052	SCV001971576	benign	not specified		no assertion criteria provided	clinical testing