ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.1354A>T (p.Thr452Ser)

gnomAD frequency: 0.00002  dbSNP: rs794729045
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183499 SCV000235959 uncertain significance not provided 2015-05-06 criteria provided, single submitter clinical testing p.Thr452Ser (ACG>TCG): c.1354 A>T in exon 8 of the JUP gene (NM_002230.2). The T452S variant has not been published as a mutation or as a benign polymorphism to our knowledge. The T452S variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is completely conserved in mammals. However, the T452S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. The variant is found in ARRHYTHMIA panel(s).
Fulgent Genetics, Fulgent Genetics RCV000765352 SCV000896617 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000765352 SCV001536486 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2021-09-02 criteria provided, single submitter clinical testing This sequence change replaces threonine with serine at codon 452 of the JUP protein (p.Thr452Ser). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with JUP-related conditions. ClinVar contains an entry for this variant (Variation ID: 201823). 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 RCV003165403 SCV003911928 uncertain significance Cardiovascular phenotype 2023-01-07 criteria provided, single submitter clinical testing The p.T452S variant (also known as c.1354A>T), located in coding exon 7 of the JUP gene, results from an A to T substitution at nucleotide position 1354. The threonine at codon 452 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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