Submissions for variant NM_004415.4(DSP):c.2596C>T (p.Arg866Cys)

gnomAD frequency: 0.00214  dbSNP: rs142429411

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038010	SCV000061676	likely benign	not specified	2015-03-23	criteria provided, single submitter	clinical testing	p.Arg866Cys in exon 18 of DSP: This variant is not expected to have clinical sig nificance because it has been identified in 0.7% (71/10402) of African chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs142429411).
GeneDx	RCV000590388	SCV000233537	likely benign	not provided	2021-03-09	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 21636032, 24503780)
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000238965	SCV000297153	uncertain significance	Arrhythmogenic right ventricular cardiomyopathy	2015-10-13	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000242786	SCV000320071	likely benign	Cardiovascular phenotype	2019-02-04	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	RCV000372307	SCV000464934	likely benign	Epidermolysis bullosa simplex due to plakophilin deficiency	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000263694	SCV000464935	likely benign	Woolly hair-skin fragility syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000318707	SCV000464936	likely benign	Lethal acantholytic epidermolysis bullosa	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000238965	SCV000464937	likely benign	Arrhythmogenic right ventricular cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV001082571	SCV000555761	benign	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2024-01-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590388	SCV000698422	likely benign	not provided	2017-03-06	criteria provided, single submitter	clinical testing	Variant summary: The DSP c.2596C>T (p.Arg866Cys) variant involves the alteration of a conserved nucleotide, resulting in a missense substitution. 4/4 in silico tools predict a damaging outcome for this variant (SNPs&GO not captured due to low reliability index). The variant resides outside of any known functional domain (InterPro). This variant was found in 75/122246 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.006826 (71/10402). This frequency is about 683 times the estimated maximal expected allele frequency of a pathogenic DSP variant (0.00001), suggesting this is likely a benign polymorphism found primarily in populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. Taken together, this variant is classified as likely benign.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000238965	SCV000747973	uncertain significance	Arrhythmogenic right ventricular cardiomyopathy	2016-11-29	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769221	SCV000900597	likely benign	Cardiomyopathy	2017-02-14	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000769221	SCV000904537	benign	Cardiomyopathy	2018-10-20	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000590388	SCV001917759	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000590388	SCV001975926	likely benign	not provided		no assertion criteria provided	clinical testing