ClinVar Miner

Submissions for variant NM_001005242.3(PKP2):c.1852G>A (p.Val618Met)

dbSNP: rs770909247
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001061843 SCV001226602 uncertain significance Arrhythmogenic right ventricular dysplasia 9 2021-11-24 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 662 of the PKP2 protein (p.Val662Met). This variant is present in population databases (rs770909247, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PKP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 856392). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 Diagnostics, LLC DBA Color Health RCV001176927 SCV001341028 likely benign Cardiomyopathy 2018-12-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV002418523 SCV002717888 likely benign Cardiovascular phenotype 2019-01-02 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx RCV003128744 SCV003805343 uncertain significance not provided 2023-02-07 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function

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