Submissions for variant NM_004415.4(DSP):c.1488G>A (p.Thr496=)

gnomAD frequency: 0.00195  dbSNP: rs35820473

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037994	SCV000061660	benign	not specified	2015-04-15	criteria provided, single submitter	clinical testing	p.Thr496Thr in exon 12 of DSP: This variant is not expected to have clinical sig nificance because it has been identified in 0.6% (60/10406) of African chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs35820473).
Invitae	RCV001086570	SCV000288527	benign	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000250673	SCV000319692	likely benign	Cardiovascular phenotype	2015-06-12	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Illumina Laboratory Services, Illumina	RCV000382508	SCV000464894	likely 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 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	RCV000328806	SCV000464896	likely 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 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	RCV000383353	SCV000464897	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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000770236	SCV000901667	likely benign	Cardiomyopathy	2016-11-11	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000770236	SCV000903640	likely benign	Cardiomyopathy	2018-03-14	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000234308	SCV001154629	likely benign	not provided	2024-04-01	criteria provided, single submitter	clinical testing	DSP: BP4, BP7
GeneDx	RCV000234308	SCV001900372	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003996333	SCV004823208	likely benign	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma	2024-02-05	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000234308	SCV001741287	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000037994	SCV001917125	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000234308	SCV001930793	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000037994	SCV001954785	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000234308	SCV001971697	likely benign	not provided		no assertion criteria provided	clinical testing