Submissions for variant NM_004415.4(DSP):c.688G>A (p.Asp230Asn)

gnomAD frequency: 0.00038  dbSNP: rs147315869

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000172532	SCV000051382	likely benign	not provided	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038081	SCV000061747	uncertain significance	not specified	2016-01-20	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Asp230Asn var iant in DSP has been reported in one adult with ARVC (Xu 2010) and two adults wi th HCM (LMM unpublished data). This variant has been identified in 48/66740 Eur opean chromosomes, including 1 homozygote, by the Exome Aggregation Consortium ( ExAC, http://exac.broadinstitute.org dbSNP rs147315869). Computational predictio n tools and conservation analysis do not provide strong support for or against a n impact to the protein. In summary, while the clinical significance of the p.As p230Asn variant is uncertain, its frequency suggests that it is more likely to be benign.
GeneDx	RCV000172532	SCV000233567	benign	not provided	2019-07-22	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 23299917, 23861362, 25351510, 20152563, 27153395, 29802319, 31402444)
Invitae	RCV001083960	SCV000288547	benign	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2024-01-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000621103	SCV000736043	benign	Cardiovascular phenotype	2017-12-05	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.
Color Diagnostics, LLC DBA Color Health	RCV000776199	SCV000911331	benign	Cardiomyopathy	2018-05-12	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001164473	SCV001326605	uncertain significance	Arrhythmogenic right ventricular dysplasia 8	2017-04-27	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	RCV000776199	SCV002043300	benign	Cardiomyopathy	2019-11-13	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000172532	SCV002821348	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	DSP: BS1, BS2
PreventionGenetics, part of Exact Sciences	RCV003944916	SCV004761887	likely benign	DSP-related condition	2019-11-11	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).