ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.1213G>A (p.Val405Ile)

gnomAD frequency: 0.00001  dbSNP: rs200019016
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000150849 SCV000198403 uncertain significance not specified 2013-10-15 criteria provided, single submitter clinical testing The Val405Ile variant in JUP has not been previously reported in individuals wit h cardiomyopathy, but has been identified in 1/192 Kenyan chromosomes by the 100 0 Genomes Project (dbSNP rs200019016). Lack of evolutionary conservation suggest s that the variant may not impact the protein, though this information is not pr edictive enough to rule out pathogenicity. Additional information is needed to f ully assess the clinical significance of the Val405Ile variant.
Invitae RCV000473876 SCV000550400 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2023-12-04 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 405 of the JUP protein (p.Val405Ile). This variant is present in population databases (rs200019016, gnomAD 0.03%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 32746448). ClinVar contains an entry for this variant (Variation ID: 163718). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Ambry Genetics RCV002354344 SCV002657160 uncertain significance Cardiovascular phenotype 2019-04-16 criteria provided, single submitter clinical testing The p.V405I variant (also known as c.1213G>A), located in coding exon 7 of the JUP gene, results from a G to A substitution at nucleotide position 1213. The valine at codon 405 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and isoleucine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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