ClinVar Miner

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

gnomAD frequency: 0.00091  dbSNP: rs142885240
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Total submissions: 22
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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, Mass General Brigham Personalized Medicine RCV000038062 SCV000061728 likely benign not specified 2020-04-20 criteria provided, single submitter clinical testing The p.Glu1740Lys variant in DSP is classified as likely benign because it has been identified in 0.2% (73/35312) of Latino and 0.18% (229/129084) of European chromosomes, including 1 homozygous individual by gnomAD (http://gnomad.broadinstitute.org). It has also been reported in >10 individuals with a range of cardiomyopathy phenotypes (ARVC, DCM, HCM, RCM, Brugada syndrome, ventricular tachycardia), and it has segregated with Brugada syndrome in 1 affected relative from 1 family (Cox 2011, Allegue 2015, Bottillo 2016, LMM data). However, these diseases have different underlying molecular mechanisms, and furthermore, several of these probands were compound or double heterozygous with a presumed pathogenic variant. In summary, this variant is likely benign due to its elevated frequency in the general population, presence of phenotypes with different underlying molecular mechanisms in reported cases, as well as cases that had other more likely causative variants identified. ACMG/AMP Criteria applied: BS1, BP5, BP4.
GeneDx RCV000172543 SCV000233547 likely benign not provided 2021-03-13 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 21606396, 31395126, 26230511, 23861362, 26656175, 27153395, 27435932, 24503780, 30821013)
Invitae RCV001082740 SCV000288543 likely benign Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2024-01-31 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000376629 SCV000465106 likely benign Lethal acantholytic epidermolysis bullosa 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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina RCV001095215 SCV000465107 likely benign 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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina RCV000406700 SCV000465109 likely benign Woolly hair-skin fragility syndrome 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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
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
Eurofins Ntd Llc (ga) RCV000172543 SCV000702977 uncertain significance not provided 2016-11-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV000621777 SCV000735617 likely benign Cardiovascular phenotype 2018-08-01 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.
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 benign Cardiomyopathy 2021-04-14 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000769232 SCV000902785 likely benign Cardiomyopathy 2018-03-16 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000172543 SCV003829146 likely benign not provided 2023-09-07 criteria provided, single submitter clinical testing
Dept of Medical Biology, Uskudar University RCV003318345 SCV004021997 uncertain significance Long QT syndrome 2024-01-08 criteria provided, single submitter research Criteria: BS1
PreventionGenetics, part of Exact Sciences RCV003974881 SCV004792821 likely benign DSP-related disorder 2023-06-14 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).
CSER _CC_NCGL, University of Washington 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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000172543 SCV001741466 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000038062 SCV001922144 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000172543 SCV001930173 likely benign not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000172543 SCV001956188 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000172543 SCV001964914 likely benign not provided no assertion criteria provided clinical testing

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