ClinVar Miner

Submissions for variant NM_004572.3(PKP2):c.928G>A (p.Val310Met) (rs768396351)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183705 SCV000236179 uncertain significance not provided 2017-06-05 criteria provided, single submitter clinical testing The V310M variant has notbeen published as pathogenic or been reported as benign to our knowledge. This variant is aconservative amino acid substitution, which is not likely to impact secondary protein structure asthese residues share similar properties. In addition, this substitution occurs at a position where aminoacids with similar properties to Valine are tolerated across species, and M310 is observed as the wildtype amino acid in at least one species (Gorilla). In silico analysis predicts this variant likely does notalter the protein structure/function. Finally, this variant is observed in 1/8642 alleles from individualsof East Asian ancestry in the ExAC dataset and also reported in 1/427 healthy control individuals(ethnicity not reported) from am ARVC study by Kapplinger et al. (2011) (Lek et al., 2016; 1000Genomes Consortium et al., 2015; Exome Variant Server).
Invitae RCV000538808 SCV000638909 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 9 2018-08-02 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 310 of the PKP2 protein (p.Val310Met). The valine residue is weakly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs768396351, ExAC 0.01%) but has not been reported in the literature in individuals with a PKP2-related disease. ClinVar contains an entry for this variant (Variation ID: 201962). 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. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000771950 SCV000904903 uncertain significance Cardiomyopathy 2019-11-21 criteria provided, single submitter clinical testing

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