ClinVar Miner

Submissions for variant NM_004572.3(PKP2):c.611G>A (p.Arg204His) (rs755215178)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000213254 SCV000270738 likely benign not specified 2015-04-06 criteria provided, single submitter clinical testing p.Arg204His in exon 3 of PKP2: This variant is not expected to have clinical sig nificance due to a lack of conservation across species, including mammals. Of no te, >20 mammals have a histidine (His) at this position despite high nearby amin o acid conservation. In addition, computational prediction tools do not suggest a high likelihood of impact to the protein. It has also been identified in 3/115 70 Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.bro adinstitute.org).
Invitae RCV000233696 SCV000288607 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 9 2018-08-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 204 of the PKP2 protein (p.Arg204His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs755215178, ExAC 0.03%) but has not been reported in the literature in individuals with a PKP2-related disease. ClinVar contains an entry for this variant (Variation ID: 201961). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function or cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Illumina Clinical Services Laboratory,Illumina RCV000318885 SCV000378469 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing

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