ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.526C>T (p.Arg176Trp)

gnomAD frequency: 0.00007  dbSNP: rs368336007
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000171963 SCV000054837 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
Blueprint Genetics RCV000208296 SCV000263961 uncertain significance Primary familial hypertrophic cardiomyopathy 2015-07-21 criteria provided, single submitter clinical testing
Ambry Genetics RCV000244325 SCV000320615 likely benign Cardiovascular phenotype 2022-02-16 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.
Invitae RCV000466475 SCV000550393 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2022-10-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 176 of the JUP protein (p.Arg176Trp). This variant is present in population databases (rs368336007, gnomAD 0.02%). This missense change has been observed in individual(s) with restrictive cardiomyopathy (PMID: 27662471). ClinVar contains an entry for this variant (Variation ID: 191675). 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.
Center of Genomic medicine, Geneva, University Hospital of Geneva RCV000499623 SCV000598142 uncertain significance Primary dilated cardiomyopathy 2016-10-26 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001198755 SCV001369750 uncertain significance Naxos disease 2020-02-25 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PP3.
GeneDx RCV000171963 SCV002567707 uncertain significance not provided 2022-05-21 criteria provided, single submitter clinical testing Reported in an individual with sudden unexplained death who also harbored a pathogenic variant in the KCNH2 gene (Sanchez et al., 2016); 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: 23861362, 27662471, 28831623, 27930701, 21859740)
Fulgent Genetics, Fulgent Genetics RCV000466475 SCV002788379 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2021-10-28 criteria provided, single submitter clinical testing

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