Submissions for variant NM_002230.4(JUP):c.460G>A (p.Glu154Lys)

gnomAD frequency: 0.00005  dbSNP: rs782765314

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000522559	SCV000617155	uncertain significance	not provided	2020-10-12	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 449256; Landrum 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: 30847666)
Invitae	RCV001212816	SCV001384414	uncertain significance	Naxos disease; Arrhythmogenic right ventricular dysplasia 12	2023-05-05	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: 449256). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 30847666). This variant is present in population databases (rs782765314, gnomAD 0.01%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 154 of the JUP protein (p.Glu154Lys).
Ambry Genetics	RCV003380597	SCV004088944	likely benign	Cardiovascular phenotype	2023-06-16	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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000522559	SCV001742555	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000522559	SCV001922160	uncertain significance	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000522559	SCV001930685	uncertain significance	not provided		no assertion criteria provided	clinical testing