ClinVar Miner

Submissions for variant NM_001005242.3(PKP2):c.1663C>A (p.Pro555Thr)

dbSNP: rs771808028
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001068780 SCV001233912 uncertain significance Arrhythmogenic right ventricular dysplasia 9 2022-09-10 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 599 of the PKP2 protein (p.Pro599Thr). This variant is present in population databases (rs771808028, gnomAD 0.02%). 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. 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. ClinVar contains an entry for this variant (Variation ID: 862118). This variant has not been reported in the literature in individuals affected with PKP2-related conditions.
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001068780 SCV001368362 uncertain significance Arrhythmogenic right ventricular dysplasia 9 2019-08-21 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2.
Color Diagnostics, LLC DBA Color Health RCV003532872 SCV004358874 uncertain significance Cardiomyopathy 2023-05-24 criteria provided, single submitter clinical testing This missense variant replaces proline with threonine at codon 599 of the PKP2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PKP2-related disorders in the literature. This variant has been identified in 7/250908 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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