Submissions for variant NM_004415.4(DSP):c.2422C>T (p.Arg808Cys)

gnomAD frequency: 0.00021  dbSNP: rs150339369

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000148478	SCV000055163	uncertain significance	Arrhythmogenic right ventricular cardiomyopathy	2018-04-05	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038008	SCV000061674	uncertain significance	not specified	2018-06-27	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Arg808Cys var iant in DSP has been reported in 6 individuals: 1 with DCM, 2 with HCM, 1 with L VH, and 2 with ARVC (Lopes 2015, Ng 2013, Al-Jassar 2011, http://arvcdatabase.in fo/, LMM unpublished data). However, this variant has been identified in 0.3% (3 0/10150) of Ashkenazi Jewish chromosomes and 35/126684 European chromosomes, inc luding 1 homozygous individual, by the Genome Aggregation Database (gnomAD, http ://gnomad.broadinstitute.org/). This variant is reported in ClinVar (Variation I D: 44874). Please note that for diseases with clinical variability, reduced pene trance, or recessive inheritance, pathogenic variants may be present at a low fr equency in the general population.Computational prediction tools and conservatio n analysis suggest that the p.Arg808Cys variant may impact the protein, though t his information is not predictive enough to determine pathogenicity. In summary, while the clinical significance of the p.Arg808Cys variant is uncertain, its fr equency in the general population suggests that it is more likely to be benign. ACMG/AMP Criteria applied: PS4_Moderate, PP3, BS1.
Ambry Genetics	RCV000622195	SCV000735485	likely benign	Cardiovascular phenotype	2017-11-30	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.
Invitae	RCV001084249	SCV000763497	likely benign	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2024-01-19	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000777603	SCV000913470	likely benign	Cardiomyopathy	2018-06-27	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000641847	SCV001154633	uncertain significance	not provided	2017-01-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001159871	SCV001321617	uncertain significance	Arrhythmogenic right ventricular dysplasia 8	2018-01-19	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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001159872	SCV001321618	uncertain significance	Lethal acantholytic epidermolysis bullosa	2018-01-19	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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001159873	SCV001321619	uncertain significance	Woolly hair-skin fragility syndrome	2018-01-19	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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000777603	SCV001333762	uncertain significance	Cardiomyopathy	2017-12-05	criteria provided, single submitter	clinical testing
CSER _CC_NCGL, University of Washington	RCV000148478	SCV000190180	uncertain significance	Arrhythmogenic right ventricular cardiomyopathy	2014-06-01	no assertion criteria provided	research