ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.902A>G (p.Glu301Gly) (rs782058451)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000208313 SCV000263964 likely pathogenic Arrhythmogenic right ventricular cardiomyopathy 2015-10-23 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000213286 SCV000271863 uncertain significance not specified 2016-01-26 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The p.Glu301Gly variant in JUP has been reported in the homozygous state in 1 individual with N axos disease (Tradakis 2014), and has also been identified in 1/66640 European c hromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute .org; dbSNP rs782058451). Computational prediction tools and conservation analys is do not provide strong support for or against an impact to the protein. In sum mary, while there is some suspicion for a pathogenic role, the clinical signific ance of the p.Glu301Gly variant is uncertain.
Invitae RCV000798524 SCV000938144 likely pathogenic Naxos disease; Arrhythmogenic right ventricular cardiomyopathy, type 12 2019-06-10 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glycine at codon 301 of the JUP protein (p.Glu301Gly). The glutamic acid residue is moderately conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is present in population databases (rs782058451, ExAC 0.002%). This variant has been observed to be homozygous in several individuals affected with Naxos disease (PMID: 28098346, 24884844). ClinVar contains an entry for this variant (Variation ID: 222662). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000996539 SCV001151299 uncertain significance not provided 2017-09-01 criteria provided, single submitter clinical testing

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