Submissions for variant NM_004415.4(DSP):c.2774G>A (p.Arg925Gln)

gnomAD frequency: 0.00013  dbSNP: rs139799237

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001256832	SCV000233600	likely benign	not provided	2019-08-22	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26383259, 26743238)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000181307	SCV000271723	uncertain significance	not specified	2015-03-18	criteria provided, single submitter	clinical testing	The p.Arg925Gln variant in DSP has not been previously reported in individuals w ith cardiomyopathy, but has been identified in up to 0.2% of chromosomes (13/667 32) from multiple ethnic groups curated by the Exome Aggregation Consortium (ExA C, http://exac.broadinstitute.org; dbSNP rs139799237). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Arg925Gln variant is uncertain.
Illumina Laboratory Services, Illumina	RCV000291383	SCV000464958	uncertain significance	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000327634	SCV000464959	uncertain significance	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000283495	SCV000464961	uncertain significance	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000456401	SCV000543281	benign	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2024-01-24	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000621213	SCV000734918	likely benign	Cardiovascular phenotype	2023-01-10	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.
Color Diagnostics, LLC DBA Color Health	RCV000777766	SCV000913734	likely benign	Cardiomyopathy	2019-10-28	criteria provided, single submitter	clinical testing
Klaassen Lab, Charite University Medicine Berlin	RCV000853132	SCV000995844	uncertain significance	Familial restrictive cardiomyopathy	2019-07-03	criteria provided, single submitter	research
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000777766	SCV001333765	likely benign	Cardiomyopathy	2023-05-26	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV001256832	SCV001433316	uncertain significance	not provided	2019-12-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001256832	SCV002586100	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	DSP: BP4
Revvity Omics, Revvity	RCV001256832	SCV003829136	uncertain significance	not provided	2022-05-20	criteria provided, single submitter	clinical testing