ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.1933G>A (p.Ala645Thr)

gnomAD frequency: 0.00003  dbSNP: rs727504778
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Total submissions: 4
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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 RCV000156095 SCV000205808 uncertain significance not specified 2013-10-18 criteria provided, single submitter clinical testing The Ala645Thr variant in JUP has not been previously reported in the individuals with cardiomyopathy and was absent from large population studies. Computationa l analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen 2, and SIFT) do not provide strong support for or against an impact to the prote in. Additional information is needed to fully assess the clinical significance o f this variant.
Invitae RCV001850147 SCV002224801 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2023-06-24 criteria provided, single submitter clinical testing This variant is present in population databases (rs727504778, gnomAD 0.02%). 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. 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. ClinVar contains an entry for this variant (Variation ID: 179306). This variant has not been reported in the literature in individuals affected with JUP-related conditions. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 645 of the JUP protein (p.Ala645Thr).
Fulgent Genetics, Fulgent Genetics RCV001850147 SCV002784536 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2021-09-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV004019870 SCV003975981 likely benign Cardiovascular phenotype 2023-05-03 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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