ClinVar Miner

Submissions for variant NM_004572.3(PKP2):c.2431C>A (p.Arg811Ser) (rs139734328)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 12
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000190558 SCV000051588 benign Arrhythmogenic right ventricular cardiomyopathy 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000038209 SCV000061877 likely benign not specified 2017-08-01 criteria provided, single submitter clinical testing
GeneDx RCV000038209 SCV000236190 uncertain significance not specified 2017-02-07 criteria provided, single submitter clinical testing p.Arg811Ser (CGC>AGC): c.2431 C>A in exon 12 of the PKP2 gene (NM_004572.3). The R811S variant of uncertain significance in the PKP2 gene has been reported previously in individuals with ARVC (Tan et al., 2010; Klauke et al., 2010; Alcalde et al., 2014), including one individual who harbored a known pathogenic variant in another ARVC-related gene (Fressar et al., 2010). However, this variant was identified in healthy control individuals (Tan et al., 2010) and the NHLBI Exome Sequencing Project and the 1000 Genomes Project identified the R811S variant with a frequency of 0.06%-0.2% of alleles of individuals of European and Mixed American ancestry, indicating it may be a rare benign variant in these populations. Additionally, the Exome Aggregation Consortium includes one individual of European ancestry who is homozygous for this variant. Nevertheless, the R811S variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. Finally, in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign. This result cannot be interpreted for diagnosis or used for family member screening at this time.The variant is found in ARVC,CARDIOMYOPATHY,ARRHYTHMIA panel(s).
Ambry Genetics RCV000244829 SCV000318609 likely benign Cardiovascular phenotype 2018-02-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000858416 SCV000557321 likely benign not provided 2019-02-21 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000458904 SCV000743445 likely benign Arrhythmogenic right ventricular cardiomyopathy, type 9 2017-06-09 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000458904 SCV000744692 likely benign Arrhythmogenic right ventricular cardiomyopathy, type 9 2017-05-31 criteria provided, single submitter clinical testing
Color RCV000776101 SCV000910922 likely benign Cardiomyopathy 2018-04-10 criteria provided, single submitter clinical testing
Mendelics RCV000458904 SCV001138676 benign Arrhythmogenic right ventricular cardiomyopathy, type 9 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000858416 SCV001148690 likely benign not provided 2017-02-01 criteria provided, single submitter clinical testing
CSER _CC_NCGL, University of Washington RCV000148730 SCV000190464 uncertain significance Arrhythmogenic right ventricular dysplasia/cardiomyopathy 2014-06-01 no assertion criteria provided research
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000458904 SCV000733154 likely benign Arrhythmogenic right ventricular cardiomyopathy, type 9 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.