ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.1582G>A (p.Val528Ile)

gnomAD frequency: 0.00018  dbSNP: rs368271628
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000767066 SCV000235961 uncertain significance not provided 2023-02-01 criteria provided, single submitter clinical testing Observed in an individual with hypertrophic cardiomyopathy who had cardiomyopathy panel testing, but it is unknown whether this individual had variants in other genes on the panel (van Lint et al., 2019); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30847666)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000183501 SCV000271861 uncertain significance not specified 2015-05-27 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Val528Ile var iant in JUP has not been previously reported in individuals with cardiomyopathy, but has been identified in 0.1% (6/7780) African chromosomes by the Exome Aggre gation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs368271628). Val ine (Val) at position 528 is conserved in mammals but not in evolutionarily dist ant species and 5 fish species carry an isoleucine (Ile), supporting that this c hange may be tolerated. Additional computational prediction tools suggest that t his variant may not impact the protein, though this information is not predictiv e enough to rule out pathogenicity. In summary, while the clinical significance of the p.Val528Ile variant is uncertain, these data suggest that it is more like ly to be benign.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000769488 SCV000900883 uncertain significance Cardiomyopathy 2017-06-22 criteria provided, single submitter clinical testing
Invitae RCV001065041 SCV001229979 likely benign Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2023-10-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV002399670 SCV002708299 likely benign Cardiovascular phenotype 2021-07-19 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 RCV001065041 SCV002788670 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2021-07-23 criteria provided, single submitter clinical testing

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