ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.522T>C (p.Cys174=) (rs144781697)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000150558 SCV000197790 benign not specified 2012-03-19 criteria provided, single submitter clinical testing p.Cys174Cys in Exon 04 of DSP: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence and has been identified in 0.3% (13/3738) of Afri can American chromosomes from a broad population by the NHLBI Exome Sequencing P roject (; dbSNP rs144781697).
Ambry Genetics RCV000251541 SCV000318427 likely benign Cardiovascular phenotype 2016-05-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Synonymous alterations with insufficient evidence to classify as benign
GeneDx RCV000150558 SCV000518101 likely benign not specified 2017-02-02 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 RCV000472500 SCV000555741 benign not provided 2019-02-04 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000150558 SCV000919284 benign not specified 2018-05-29 criteria provided, single submitter clinical testing Variant summary: DSP c.522T>C alters a non-conserved nucleotide resulting in a synonymous change. The variant allele was found at a frequency of 0.00041 in 277036 control chromosomes, predominantly at a frequency of 0.0046 within the African subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within African control individuals in the gnomAD database is approximately 184 fold of the estimated maximal expected allele frequency for a pathogenic variant in DSP causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.522T>C in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.

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