Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000586645 | SCV000699462 | uncertain significance | not provided | 2017-01-23 | criteria provided, single submitter | clinical testing | Variant summary: The JUP c.1606C>G (p.Gln536Glu) variant located in the Armadillo-type fold domain (via InterPro) causes a missense change involving a conserved nucleotide, which 2/4 in silico tools predict a benign outcome, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 1/81916, which does not exceed the estimated maximal expected allele frequency for a pathogenic JUP variant of 1/40000. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. Therefore, until additional information becomes available (ie, clinical and functional studies), the variant of interest has been classified as a "Variant of Uncertain Significance (VUS)." |
Invitae | RCV002530941 | SCV003500071 | uncertain significance | Naxos disease; Arrhythmogenic right ventricular dysplasia 12 | 2023-05-09 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 496449). This variant has not been reported in the literature in individuals affected with JUP-related conditions. This variant is present in population databases (rs782683108, gnomAD 0.02%). This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 536 of the JUP protein (p.Gln536Glu). |