ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.1876G>A (p.Ala626Thr)

gnomAD frequency: 0.00001  dbSNP: rs782547688
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183505 SCV000235965 uncertain significance not provided 2019-01-22 criteria provided, single submitter clinical testing The A626T variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The A626T 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. The A626T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.
Invitae RCV000472032 SCV000550391 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2022-07-12 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 201828). This variant has not been reported in the literature in individuals affected with JUP-related conditions. This variant is present in population databases (rs782547688, gnomAD 0.003%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 626 of the JUP protein (p.Ala626Thr).
Ambry Genetics RCV002408807 SCV002723242 uncertain significance Cardiovascular phenotype 2019-04-04 criteria provided, single submitter clinical testing The p.A626T variant (also known as c.1876G>A), located in coding exon 10 of the JUP gene, results from a G to A substitution at nucleotide position 1876. The alanine at codon 626 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. 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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