ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.1565C>T (p.Ala522Val)

gnomAD frequency: 0.00010  dbSNP: rs1060502679
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000475805 SCV000550403 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2022-09-29 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 522 of the JUP protein (p.Ala522Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with sudden unexplained death (PMID: 29247119). ClinVar contains an entry for this variant (Variation ID: 409989). 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. 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 RCV000618384 SCV000738042 uncertain significance Cardiovascular phenotype 2022-01-04 criteria provided, single submitter clinical testing The p.A522V variant (also known as c.1565C>T), located in coding exon 8 of the JUP gene, results from a C to T substitution at nucleotide position 1565. The alanine at codon 522 is replaced by valine, an amino acid with similar properties. This amino acid position is not well conserved in available 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.
GeneDx RCV001799663 SCV002043799 uncertain significance not provided 2021-06-24 criteria provided, single submitter clinical testing Reported as a variant of uncertain significance, among a cohort of individuals with sudden unexplained death (Lin Y et al., 2017); Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID 409989; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 27535533, 29247119)

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