ClinVar Miner

Submissions for variant NM_004572.3(PKP2):c.826C>T (p.Pro276Ser) (rs201944276)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000244304 SCV000318036 likely benign Cardiovascular phenotype 2017-06-12 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 RCV000172583 SCV000051040 likely benign not provided 2013-06-24 criteria provided, single submitter research
GeneDx RCV000154802 SCV000236178 likely benign not specified 2016-03-29 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.
Invitae RCV000640030 SCV000761617 likely benign Arrhythmogenic right ventricular cardiomyopathy, type 9 2017-09-28 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000154802 SCV000204482 uncertain significance not specified 2014-08-08 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Pro276Ser varia nt in PKP2 has not been reported in individuals with cardiomyopathy but was iden tified in 1/1093 chromosomes by the ClinSeq project and in 2/8600 European Ameri can chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington. edu/EVS/; dbSNP rs201944276). Proline (Pro) at position 276 is not conserved in mammals and evolutionarily distant species and the change to Serine (Ser) is pre sent in 6 mammals including hamster, bushbaby, dolphin, killer whale, tenrec and tasmanian devil; however, the local alignment of this region is poor. Additiona l computational prediction tools indicate this variant may not impact the protei n, though this information is not predictive enough to rule out pathogenicity. I n summary, while the clinical significance of the Pro276Ser variant is uncertain , conservation data suggest that it is more likely to be benign.

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