ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.1982G>A (p.Arg661Gln) (rs555499592)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000757415 SCV000885624 uncertain significance not provided 2018-04-20 criteria provided, single submitter clinical testing The JUP c.1982G>A; p.Arg661Gln variant (rs555499592, ClinVar variant ID 409985), to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the genome Aggregation Database (gnomAD) with an overall population frequency of 0.1% (identified on 27 out of 18,870 chromosomes). The arginine at position 661 is moderately conserved, considering 13 species, and computational analyses of the effects of the p.Arg661Gln variant on protein structure and function do not predict a deleterious effect (SIFT: tolerated, PolyPhen-2: benign). Based on the available information, the clinical significance of the p.Arg661Gln variant cannot be determined with certainty.
Invitae RCV000473901 SCV000550397 uncertain significance Naxos disease; Arrhythmogenic right ventricular cardiomyopathy, type 12 2016-11-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 661 of the JUP protein (p.Arg661Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs555499592, ExAC 0.1%) but has not been reported in the literature in individuals with a JUP-related disease. 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, and is found in the population at an appreciable frequency. This variant is not anticipated to cause disease; however, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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