Submissions for variant NM_004415.4(DSP):c.3696C>A (p.Ser1232=)

gnomAD frequency: 0.00132  dbSNP: rs141120358

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038030	SCV000061696	likely benign	not specified	2012-03-15	criteria provided, single submitter	clinical testing	Ser1232Ser in exon 23 of DSP: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. This variant has been identified in 0.2% (8/37 38) of African American chromosomes from a broad population by the NHLBI Exome S equencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs141120358). Ser123 2Ser in exon 23 of DSP (rs141120358; allele frequency = 0.2%, 8/3738) **
Eurofins Ntd Llc (ga)	RCV000038030	SCV000228051	likely benign	not specified	2014-12-16	criteria provided, single submitter	clinical testing
GeneDx	RCV000038030	SCV000512879	benign	not specified	2015-09-18	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV001081739	SCV000555773	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	RCV000589193	SCV000698433	benign	not provided	2016-04-05	criteria provided, single submitter	clinical testing	Variant Summary: The variant of interest causes a synonymous change involving a non-conserved nucleotide with 5/5 in silico programs via Alamut predicting no significant effect on splicing, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 55/120418 (1/2189), predominantly in the African cohort, 52/10138 (1/194), which exceeds the predicted maximum expected allele frequency for a pathogenic DSP variant of 1/100000. Therefore, suggesting that the variant is a common polymorphism found in population(s) of African origin. In addition, multiple reputable clinical laboratories cite the variant with a classification of "likely benign." Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Benign.
Ambry Genetics	RCV000617930	SCV000737006	likely benign	Cardiovascular phenotype	2015-09-28	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	RCV000771834	SCV000904547	benign	Cardiomyopathy	2018-09-16	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000589193	SCV002049083	likely benign	not provided	2021-04-13	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003964856	SCV004785774	likely benign	DSP-related disorder	2021-09-10	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).