ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.5218G>A (p.Glu1740Lys) (rs142885240)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000172543 SCV000051388 likely benign not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000038062 SCV000061728 uncertain significance not specified 2017-05-19 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Glu1740Lys va riant in DSP has been reported in >10 individuals with a range of phenotypes (AR VC, DCM, HCM, RCM, Brugada syndrome, ventricular tachycardia), segregated with B rugada syndrome in 1 affected relative from 1 family (Cox 2011, Allegue 2015, Bo ttillo 2016, LMM data). However, several of these probands were compound or doub le heterozygous with a presumed pathogenic variant and 1 of the affected familie s with Brugada syndrome had two relatives that carried this variant and were rep ortedly unaffected. This variant has also been identified in 0.22% (74/34342) of Latino and 0.18% (225/126622) of European chromosomes, including 1 homozygous i ndividual, by the genome Aggregation Database (gnomAD, http://gnomad.broadinstit ute.org/; dbSNP rs142885240). Computational prediction tools and conservation an alysis suggest that the p.Glu1740Lys variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, while the clinical significance of the p.Glu1740Lys variant is uncertain, its f requency and association with disorders with different underlying molecular mech anisms suggests that it is more likely to be benign.
GeneDx RCV000038062 SCV000233547 likely benign not specified 2018-01-16 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 RCV000172543 SCV000288543 likely benign not provided 2019-02-19 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000376629 SCV000465106 likely benign Epidermolysis bullosa, lethal acantholytic 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000291666 SCV000465107 likely benign Arrhythmogenic right ventricular cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000346661 SCV000465108 likely benign Ectodermal dysplasia skin fragility syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000406700 SCV000465109 likely benign Skin fragility woolly hair syndrome 2016-06-14 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000415071 SCV000492553 uncertain significance Primary dilated cardiomyopathy; Migraine; Hemiplegia 2014-11-24 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000172543 SCV000702977 uncertain significance not provided 2016-11-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV000621777 SCV000735617 likely benign Cardiovascular phenotype 2017-06-28 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Subpopulation frequency in support of benign classification
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000038062 SCV000747953 uncertain significance not specified 2017-01-26 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769232 SCV000900608 likely benign Cardiomyopathy 2017-05-08 criteria provided, single submitter clinical testing
Color RCV000769232 SCV000902785 likely benign Cardiomyopathy 2018-03-16 criteria provided, single submitter clinical testing
CSER_CC_NCGL; University of Washington Medical Center RCV000291666 SCV000503539 likely benign Arrhythmogenic right ventricular cardiomyopathy 2016-08-01 no assertion criteria provided research Found in patient having exome sequencing for an unrelated indication. No known history of arrhythmogenic right ventricular dysplasia.

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