ClinVar Miner

Submissions for variant NM_004572.3(PKP2):c.505A>G (p.Ser169Gly) (rs139139859)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000617259 SCV000735915 likely benign Cardiovascular phenotype 2017-07-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Subpopulation frequency in support of benign classification,In silico models in agreement (benign)
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000172585 SCV000051416 likely benign not provided 2013-06-24 criteria provided, single submitter research
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769394 SCV000900786 uncertain significance Cardiomyopathy 2015-09-11 criteria provided, single submitter clinical testing
CSER_CC_NCGL; University of Washington Medical Center RCV000148728 SCV000190462 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2014-06-01 criteria provided, single submitter research Low GERP score may suggest that this variant may belong in a lower pathogenicity class
Color RCV000769394 SCV000910881 likely benign Cardiomyopathy 2018-03-13 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000464777 SCV000744713 likely benign Arrhythmogenic right ventricular cardiomyopathy, type 9 2017-05-31 criteria provided, single submitter clinical testing
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000148728 SCV000257986 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2015-02-13 criteria provided, single submitter clinical testing
GeneDx RCV000038222 SCV000236206 likely benign not specified 2017-11-16 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.
Institute for Genomic Medicine (IGM) Clinical Laboratory,Nationwide Children's Hospital RCV000038222 SCV000864291 likely benign not specified 2017-08-25 criteria provided, single submitter clinical testing BS1, BP4; This alteration has an allele frequency that is greater than expected for the associated disease, and is predicted to be tolerated by multiple functional prediction tools.
Integrated Genetics/Laboratory Corporation of America RCV000038222 SCV000918023 likely benign not specified 2017-11-27 criteria provided, single submitter clinical testing Variant summary: The PKP2 c.505A>G (p.Ser169Gly) variant involves the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 308/277798 control chromosomes (gnomAD and literature), predominantly observed in the South Asian subpopulation at a frequency of 0.00234 (72/30772). This frequency is about 5 times the estimated maximal expected allele frequency of a pathogenic PKP2 variant (0.0004301), suggesting this is likely a benign polymorphism found primarily in the populations of South Asian origin. In addition, ExAC reports 1 homozygous occurrence, however the clinical status of this individual is unknown. This variant was reported in patients with DCM, ARVC, complex arrhythmias of RV origin, and SADS without strong evidence for causality. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. Taken together, this variant is classified as likely benign.
Invitae RCV000464777 SCV000557319 likely benign Arrhythmogenic right ventricular cardiomyopathy, type 9 2018-01-06 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000038222 SCV000061890 likely benign not specified 2015-07-01 criteria provided, single submitter clinical testing p.Ser169Gly in exon 3 of PKP2: This variant has been reported in 1 athlete with features of ARVC and at least 1 individual with DCM (La Gerche 2010, Elliott 201 0), as well as in 3 individuals tested by our laboratory with cardiomyopathy and /or conduction system disease. However, this variant is not expected to have cli nical significance due to a lack of conservation across species, including mamma ls. Of note, 8 mammals have a glycine (Gly) at this position despite high nearby amino acid conservation. This variant has also been detected in 0.2% (39/16494) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://ex ac.broadinstitute.org; dbSNP rs139139859). Although a modifying role cannot be e xcluded, the presence of the variant amino acid in multiple mammals and its freq uency in the general population all support that it is likely benign.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000172585 SCV000987327 likely benign not provided criteria provided, single submitter clinical testing
Stanford Center for Inherited Cardiovascular Disease,Stanford University RCV000038222 SCV000280416 uncertain significance not specified 2014-10-16 no assertion criteria provided clinical testing Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease

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