Total submissions: 6
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, |
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, |
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, |
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, |
RCV000234226 | SCV002817060 | uncertain significance | Naxos disease; Arrhythmogenic right ventricular dysplasia 12 | 2021-10-18 | criteria provided, single submitter | clinical testing |