ClinVar Miner

Submissions for variant NM_004572.3(PKP2):c.2303A>C (p.Lys768Thr) (rs201487421)

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Total submissions: 3
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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 RCV000172086 SCV000054792 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
Invitae RCV000705511 SCV000834511 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 9 2018-06-13 criteria provided, single submitter clinical testing This sequence change replaces lysine with threonine at codon 768 of the PKP2 protein (p.Lys768Thr). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and threonine. This variant is present in population databases (rs201487421, ExAC 0.1%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with PKP2-related disease. ClinVar contains an entry for this variant (Variation ID: 191764). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV001191380 SCV001359192 likely benign Cardiomyopathy 2019-10-16 criteria provided, single submitter clinical testing

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