ClinVar Miner

Submissions for variant NM_004572.3(PKP2):c.1093A>G (p.Met365Val) (rs143900944)

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Total submissions: 6
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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 RCV000172090 SCV000051039 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
Color RCV000777990 SCV000914096 likely benign Cardiomyopathy 2018-08-13 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000457033 SCV000733166 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 9 no assertion criteria provided clinical testing
GeneDx RCV000151659 SCV000236182 likely benign not specified 2017-04-24 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 RCV000457033 SCV000557315 likely benign Arrhythmogenic right ventricular cardiomyopathy, type 9 2017-11-08 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000151659 SCV000199929 likely benign not specified 2016-03-21 criteria provided, single submitter clinical testing Met365Val in exon 4 of PKP2: This variant is not expected to have clinical signi ficance due to a lack of conservation across species, including mammals. Of note , multiple mammals (mouse, rat, horse, and elephant) have a valine (Val) at this position despite high nearby amino acid conservation. In addition, computationa l analyses do not suggest a high likelihood of impact to the protein. This varia nt has also been identified in 0.1% (20/16512) of South Asian chromosomes, inclu ding one homozygote, by the Exome Aggregation Consortium (ExAC, http://exac.broa dinstitute.org; dbSNP rs143900944). Additionally, this variant has been reported in one individual with Brugada snydrome, and in vitro functional studies sugges t this variant may impact protein function (Cerrone 2014); however, these types of assays may not accurately represent biological function. However, the lack of conservation and the frequency in controls suggests that it is likely to be ben ign.

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