ClinVar Miner

Submissions for variant NM_004572.3(PKP2):c.1592T>G (p.Ile531Ser) (rs147240502)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000439244 SCV000885968 benign not provided 2017-06-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV000249816 SCV000318195 benign Cardiovascular phenotype 2015-08-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Biesecker Lab/Human Development Section,National Institutes of Health RCV000172579 SCV000054794 likely benign Arrhythmogenic right ventricular cardiomyopathy 2013-06-24 criteria provided, single submitter research
Blueprint Genetics, RCV000038174 SCV000207154 likely benign not specified 2015-05-27 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770412 SCV000901855 likely benign Cardiomyopathy 2016-01-07 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000439244 SCV000510680 likely benign not provided 2016-09-16 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
Color RCV000770412 SCV000910882 benign Cardiomyopathy 2018-03-13 criteria provided, single submitter clinical testing
GeneDx RCV000038174 SCV000171016 benign not specified 2013-01-25 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.
Illumina Clinical Services Laboratory,Illumina RCV000172579 SCV000378453 likely benign Arrhythmogenic right ventricular cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000439244 SCV000698463 benign not provided 2016-09-12 criteria provided, single submitter clinical testing Variant summary: The PKP2 c.1592T>G (p.Ile531Ser) variant causes a missense change with 3/3 in silico tools (SNPs&GO and Mutation Taster not captured due to low reliability index and p-value, respectively) predict a damaging outcome for this variant. This variant was found in 867/136406 control chromosomes (2 homozygotes) at a frequency of 0.006356, which is approximately 15 times the estimated maximal expected allele frequency of a pathogenic PKP2 variant (0.0004301), suggesting this variant is likely a benign polymorphism. In addition, multiple publications report the variant to co-occur with other potentially pathogenic variants. In the few small pedigrees published, the variant did not segregate within families, leading authors to conclude that this variant could be modulating the effect of another variant or this variant could have low penetrance. Furthermore, functional studies support the variant to have comparable to wild-type function. In addition, multiple reputable clinical diagnostic laboratories cite the variant as "likely benign/benign." Therefore, taking all available lines of evidence into consideration, the variant of interest has been classified as Benign.
Invitae RCV000231874 SCV000288595 benign Arrhythmogenic right ventricular cardiomyopathy, type 9 2017-12-29 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000038174 SCV000061840 benign not specified 2015-04-08 criteria provided, single submitter clinical testing p.Ile531Ser in exon 7 of PKP2: This variant is not expected to have clinical significance because it has been identified in 2.6% (170/6614) of Finnish chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs147240502).

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