ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.809T>A (p.Leu270Gln)

gnomAD frequency: 0.00008  dbSNP: rs794729040
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000692331 SCV000820147 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2024-01-04 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 270 of the JUP protein (p.Leu270Gln). This variant is present in population databases (rs374177985, gnomAD 0.007%). 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: 201818). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001264511 SCV001442701 uncertain significance not specified 2020-10-19 criteria provided, single submitter clinical testing Variant summary: JUP c.809T>A (p.Leu270Gln) results in a non-conservative amino acid change located in the Armadillo-like helical domain (IPR011989) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 251430 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.809T>A in individuals affected with Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, citing the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
AiLife Diagnostics, AiLife Diagnostics RCV002223809 SCV002502308 uncertain significance not provided 2022-02-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV002415782 SCV002678208 likely benign Cardiovascular phenotype 2023-04-18 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 RCV000692331 SCV002787068 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2021-07-28 criteria provided, single submitter clinical testing

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