Submissions for variant NM_004415.4(DSP):c.5498A>T (p.Glu1833Val)

gnomAD frequency: 0.00908  dbSNP: rs78652302

Total submissions: 25

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000038065	SCV000051539	benign	not specified	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038065	SCV000061731	benign	not specified	2012-02-23	criteria provided, single submitter	clinical testing	Glu1833Val in exon 24 of DSP: This variant is not expected to have clinical sign ificance because it has been reported in multiple studies and in dbSNP at a freq uency of ~1% (Barahona-Dussault 2010, Gehmlich 2011, Garcia-Pavia 2011, Quarta 2 011, dbSNP rs78652302). In addition, this variant has been identified in 1.3% (9 2/7020) of European American chromosomes from a broad population by the NHLBI Ex ome Sequencing Project (http://evs.gs.washington.edu/EVS).
GeneDx	RCV000038065	SCV000168268	benign	not specified	2013-06-08	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	RCV001082506	SCV000288544	benign	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2024-01-31	criteria provided, single submitter	clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000238901	SCV000297159	benign	Arrhythmogenic right ventricular cardiomyopathy	2015-07-29	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000038065	SCV000310365	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000385269	SCV000465123	likely benign	Woolly hair-skin fragility syndrome	2018-04-05	criteria provided, single submitter	clinical testing	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, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000290923	SCV000465124	likely benign	Lethal acantholytic epidermolysis bullosa	2018-04-05	criteria provided, single submitter	clinical testing	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, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV001095253	SCV000465125	likely benign	Arrhythmogenic right ventricular dysplasia 8	2018-04-05	criteria provided, single submitter	clinical testing	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, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000588812	SCV000603390	benign	not provided	2023-10-23	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588812	SCV000698441	benign	not provided	2016-01-13	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000038065	SCV000703512	benign	not specified	2016-12-09	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000621155	SCV000734881	benign	Cardiovascular phenotype	2015-06-18	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769233	SCV000900609	benign	Cardiomyopathy	2017-08-23	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000769233	SCV000902706	benign	Cardiomyopathy	2018-03-15	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000238901	SCV000987323	likely benign	Arrhythmogenic right ventricular cardiomyopathy	2016-12-22	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852997	SCV000995749	benign	Cardiomyopathy; Long QT syndrome; Hypertrophic cardiomyopathy	2017-10-25	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000588812	SCV001249743	benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	DSP: BP4, BS1, BS2
Fulgent Genetics, Fulgent Genetics	RCV002496607	SCV002807911	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	2021-09-28	criteria provided, single submitter	clinical testing
Stanford Center for Inherited Cardiovascular Disease, Stanford University	RCV000038065	SCV000280092	uncertain significance	not specified	2011-08-25	no assertion criteria provided	clinical testing	Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. This variant has been reported in one proband with ARVC who was homozygous for the variant and had no additional variants in the four desmosomal genes that were tested (PKP2, DSP, DSG2 and DSC2) (Brahona-Dussault et al 2010). Notably, the authors list the variant as a polymorphism with a minor allele frequency of 1.5%, though it is unclear where this allele frequency estimate is derived from. There is no segregation data on this variant. This is a non conservative amino acid change with a polar, negative Glutamic acid replaced with a nonpolar, neutral Valine. In silico analysis report conflicting results: SIFT predicts the amino acid change to be tolerated PolyPhen predicts the change to be possibly damaging. It is listed in dbSNP (rs 78652302). In a sample of 2276 individuals, 1.6% were heterozygous for the variant. No homozygotes were reported. Variants in DSP have not been linked to HCM, though they have been linked to both ARVC and DCM.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000588812	SCV001741774	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000038065	SCV001925454	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000038065	SCV001929040	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000038065	SCV001956808	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000038065	SCV001976327	benign	not specified		no assertion criteria provided	clinical testing