Submissions for variant NM_002230.4(JUP):c.2167_2172del (p.Asp723_Tyr724del)

gnomAD frequency: 0.00006  dbSNP: rs782439900

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000348471	SCV000402698	uncertain significance	Naxos disease	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000394661	SCV000402699	uncertain significance	Arrhythmogenic right ventricular cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000657981	SCV000779752	uncertain significance	not provided	2018-04-04	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the JUP gene. The c.2167_2172delGACTAC variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is observed at a global allele frequency of 10/275930 (0.004%) alleles in large population cohorts, including 3/23970 (0.013%) alleles from individuals of African ancestry (Lek et al., 2016). The c.2167_2172delGACTAC variant is predicted to result in the in-frame deletion of two amino acids, denoted p.Asp723_Tyr724del. However, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function.
Invitae	RCV000824161	SCV000965047	uncertain significance	Naxos disease; Arrhythmogenic right ventricular dysplasia 12	2023-12-06	criteria provided, single submitter	clinical testing	This variant, c.2167_2172del, results in the deletion of 2 amino acid(s) of the JUP protein (p.Asp723_Tyr724del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs782439900, gnomAD 0.01%). 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: 323162). 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	RCV002429281	SCV002731346	likely benign	Cardiovascular phenotype	2021-07-06	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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003150161	SCV003838223	uncertain significance	Cardiomyopathy	2022-05-19	criteria provided, single submitter	clinical testing