ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.607C>T (p.Arg203Cys)

gnomAD frequency: 0.00004  dbSNP: rs147354282
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000234226 SCV000287316 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2023-10-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 203 of the JUP protein (p.Arg203Cys). This variant is present in population databases (rs147354282, gnomAD 0.01%). 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: 239107). 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 RCV000780357 SCV000917549 uncertain significance not specified 2018-06-11 criteria provided, single submitter clinical testing Variant summary: JUP c.607C>T (p.Arg203Cys) results in a non-conservative amino acid change located in one of the Armadillo repeats (IPR000225) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6.2e-05 in 273732 control chromosomes (in gnomAD). The observed variant frequency is approximately 6.2 fold of the estimated maximal expected allele frequency for a pathogenic variant in JUP causing Arrhythmia phenotype (1e-05), suggesting that the variant is benign. To our knowledge, no occurrence of c.607C>T in individuals affected with Arrhythmia 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, and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Illumina Laboratory Services, Illumina RCV001124846 SCV001283843 uncertain significance Naxos disease 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina RCV001124847 SCV001283844 uncertain significance Arrhythmogenic right ventricular dysplasia 12 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Ambry Genetics RCV002354649 SCV002654736 likely benign Cardiovascular phenotype 2022-05-13 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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 RCV000234226 SCV002817060 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2021-10-18 criteria provided, single submitter clinical testing

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