ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.1039G>A (p.Ala347Thr)

gnomAD frequency: 0.00005  dbSNP: rs782301706
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000221503 SCV000279551 uncertain significance not provided 2015-11-12 criteria provided, single submitter clinical testing The A347T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This 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 A347T 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. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, no missense variants in nearby residues have been reported in the Human Gene Mutation Database (Stenson et al., 2014).
Invitae RCV000810541 SCV000950752 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2023-11-24 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 347 of the JUP protein (p.Ala347Thr). This variant is present in population databases (rs782301706, gnomAD 0.004%). This missense change has been observed in individual(s) with cardiomyopathy (PMID: 30847666). ClinVar contains an entry for this variant (Variation ID: 234601). 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 disruptive. 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 RCV002390589 SCV002701137 likely benign Cardiovascular phenotype 2021-09-03 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.
Fulgent Genetics, Fulgent Genetics RCV000810541 SCV002794383 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2021-08-17 criteria provided, single submitter clinical testing

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