ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.527G>T (p.Arg176Leu)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002344447 SCV002643009 uncertain significance Cardiovascular phenotype 2020-03-16 criteria provided, single submitter clinical testing The p.R176L variant (also known as c.527G>T), located in coding exon 3 of the JUP gene, results from a G to T substitution at nucleotide position 527. The arginine at codon 176 is replaced by leucine, an amino acid with dissimilar properties. Another alteration affecting the same amino acid, p.R176W (c.526C>T), has been reported in association with cardiomyopathy (Kostareva A et al. PLoS ONE Sep;11:e0163362). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV003096678 SCV002938940 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2022-04-07 criteria provided, single submitter clinical testing 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 tolerated. This variant has not been reported in the literature in individuals affected with JUP-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 176 of the JUP protein (p.Arg176Leu).

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