ClinVar Miner

Submissions for variant NM_001005242.3(PKP2):c.1445C>T (p.Thr482Met) (rs146882581)

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Total submissions: 20
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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 RCV000038172 SCV000051418 benign not specified 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000038172 SCV000061838 likely benign not specified 2015-06-25 criteria provided, single submitter clinical testing p.Thr526Met in exon 7 of PKP2: This variant is not expected to have clinical sig nificance because it has been identified in 0.6% (60/10364) of African chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs146882581).
Invitae RCV000205511 SCV000261983 benign Arrhythmogenic right ventricular dysplasia 9 2020-12-06 criteria provided, single submitter clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000239283 SCV000297166 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2015-10-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV000621305 SCV000734898 likely benign Cardiovascular phenotype 2018-09-27 criteria provided, single submitter clinical testing In silico models in agreement (benign);Subpopulation frequency in support of benign classification
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000038172 SCV000740391 likely benign not specified 2016-10-18 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000205511 SCV000743455 likely benign Arrhythmogenic right ventricular dysplasia 9 2014-10-09 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000205511 SCV000744700 likely benign Arrhythmogenic right ventricular dysplasia 9 2015-09-21 criteria provided, single submitter clinical testing
Institute for Genomic Medicine (IGM) Clinical Laboratory,Nationwide Children's Hospital RCV000038172 SCV000864297 likely benign not specified 2017-08-14 criteria provided, single submitter clinical testing BS1, BP4, BP6; This alteration has an allele frequency that is greater than expected for the associated disease, is predicted to be tolerated by multiple functional prediction tools, and was reported as a benign/likely benign alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory).
Color Health, Inc RCV000771145 SCV000902955 likely benign Cardiomyopathy 2018-03-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000038172 SCV000920009 likely benign not specified 2018-06-04 criteria provided, single submitter clinical testing Variant summary: PKP2 c.1577C>T (p.Thr526Met) results in a non-conservative amino acid change located in the Armadillo-type fold (IPR016024) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0024 in 278492 control chromosomes in the gnomAD database, including 4 homozygotes. The observed variant frequency is approximately 5.7 fold of the estimated maximal expected allele frequency for a pathogenic variant in PKP2 causing Arrhythmia phenotype (0.00043), strongly suggesting that the variant is benign. c.1577C>T has been reported in the literature in individuals affected with Arrhythmia. These data do not allow any conclusion about variant significance. Co-occurrences with other pathogenic variant(s) have been reported (PKP2, p.L452*; DSP c.969_974delAAAAGA, p.E324_K325del; DES c.359C>A, p.A120D), providing supporting evidence for a benign role. (Rasmussen 2014, Rasmussen 2013, Brodehl 2013). These authors proposed that the variant of interest might modify the phenotype of other pathogenic variants (Rasmussen 2013) although no conclusive evidence supporting this notion has been published. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as benign (1x), likely benign (4x) or VUS (1x). Based on the evidence outlined above, the variant was classified as likely benign.
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852676 SCV000995383 benign Brugada syndrome; Premature ventricular contraction 2019-01-10 criteria provided, single submitter clinical testing
Mendelics RCV000205511 SCV001138680 benign Arrhythmogenic right ventricular dysplasia 9 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000205511 SCV001269794 likely benign Arrhythmogenic right ventricular dysplasia 9 2018-01-26 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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000771145 SCV001333850 benign Cardiomyopathy 2017-12-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000205511 SCV001473706 benign Arrhythmogenic right ventricular dysplasia 9 2020-06-23 criteria provided, single submitter clinical testing
GeneDx RCV001705683 SCV001869177 benign not provided 2018-12-11 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 26332594, 27153395, 26764160, 21636032, 25637381, 23299917)
CSER _CC_NCGL, University of Washington RCV000148726 SCV000190458 likely benign Familial isolated arrhythmogenic right ventricular dysplasia 2014-06-01 no assertion criteria provided research
Clinical Genetics,Academic Medical Center RCV000038172 SCV001919682 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000038172 SCV001953405 benign not specified no assertion criteria provided clinical testing

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