Submissions for variant NM_002230.4(JUP):c.352G>A (p.Glu118Lys)

gnomAD frequency: 0.00011  dbSNP: rs149004293

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000171964	SCV000050951	uncertain significance	not provided	2013-06-24	criteria provided, single submitter	research
GeneDx	RCV000171964	SCV000536629	uncertain significance	not provided	2019-09-12	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Observed in 0.0066% (18/271148) of global alleles in large population cohorts (Lek et al., 2016); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 191676; Landrum et al., 2016); Reported as a variant of uncertain significance in one individual from a cohort of individuals not selected for cardiomyopathy, arrhythmia, or family history of sudden cardiac death, who underwent exome sequencing (Ng et al., 2013); This variant is associated with the following publications: (PMID: 23861362)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000705755	SCV000834768	uncertain significance	Naxos disease; Arrhythmogenic right ventricular dysplasia 12	2024-12-06	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 118 of the JUP protein (p.Glu118Lys). This variant is present in population databases (rs149004293, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with JUP-related conditions. ClinVar contains an entry for this variant (Variation ID: 191676). 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. 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.
Ambry Genetics	RCV002453594	SCV002616147	benign	Cardiovascular phenotype	2022-08-11	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Fulgent Genetics, Fulgent Genetics	RCV000705755	SCV002793781	uncertain significance	Naxos disease; Arrhythmogenic right ventricular dysplasia 12	2021-07-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000171964	SCV004562412	uncertain significance	not provided	2023-08-16	criteria provided, single submitter	clinical testing	The JUP c.352G>A; p.Glu118Lys variant (rs149004293), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 191676). This variant is found in the African/African-American population with an allele frequency of 0.0549% (13/23,676 alleles) in the Genome Aggregation Database. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.4). Due to limited information, the clinical significance of this variant is uncertain at this time.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV005237639	SCV005885017	likely benign	not specified	2024-12-20	criteria provided, single submitter	clinical testing
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000678710	SCV000804875	uncertain significance	Left ventricular hypertrophy	2016-01-22	no assertion criteria provided	clinical testing