ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.1372G>A (p.Ala458Thr)

gnomAD frequency: 0.00009  dbSNP: rs139559495
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489721 SCV000577061 uncertain significance not provided 2023-09-19 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23396983, 25351510)
Invitae RCV000546052 SCV000645725 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2022-09-26 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 458 of the JUP protein (p.Ala458Thr). This variant is present in population databases (rs139559495, gnomAD 0.03%). 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: 426584). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 RCV000621825 SCV000735783 likely benign Cardiovascular phenotype 2022-12-22 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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