ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.4489C>T (p.Arg1497Trp) (rs148041814)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000038045 SCV000061711 likely benign not specified 2012-02-09 criteria provided, single submitter clinical testing Arg1497Trp in exon 23 of DSP: This variant is not expected to have clinical sign ificance because it has been identified in 0.4% (17/3738) of African American ch romosomes by the NHLBI Exome Sequencing Project in a broad population (http://ev; dbSNP rs148041814). Arg1497Trp in exon 23 of DSP (rs14 8041814; allele frequency = 0.4%, 17/3738) **
GeneDx RCV000038045 SCV000168266 benign not specified 2014-04-25 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.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000202877 SCV000257967 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2015-06-08 criteria provided, single submitter clinical testing
Invitae RCV001080732 SCV000288539 likely benign Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2020-12-08 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000038045 SCV000333271 likely benign not specified 2015-08-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV000619831 SCV000736005 likely benign Cardiovascular phenotype 2018-10-04 criteria provided, single submitter clinical testing Subpopulation frequency in support of benign classification
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770246 SCV000901677 likely benign Cardiomyopathy 2017-08-02 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000845533 SCV000987647 uncertain significance not provided criteria provided, single submitter clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852995 SCV000995746 likely benign Restrictive cardiomyopathy 2018-08-13 criteria provided, single submitter clinical testing
Color Health, Inc RCV000770246 SCV001358195 benign Cardiomyopathy 2018-07-03 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000038045 SCV001363279 benign not specified 2019-12-09 criteria provided, single submitter clinical testing Variant summary: DSP c.4489C>T (p.Arg1497Trp) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00033 in 250336 control chromosomes, predominantly at a frequency of 0.0047 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 24-folds over the estimated maximal expected allele frequency for a pathogenic variant in DSP causing Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy phenotype (0.0002), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. Six ClinVar submissions (evaluation after 2014) cites the variant five times as likely benign and once as uncertain significance. Based on the evidence outlined above, the variant was classified as benign.

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