Submissions for variant NM_002230.4(JUP):c.916del (p.Ile306fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002378858	SCV002686153	uncertain significance	Cardiovascular phenotype	2022-07-19	criteria provided, single submitter	clinical testing	The c.916delA variant, located in coding exon 5 of the JUP gene, results from a deletion of one nucleotide at nucleotide position 916, causing a translational frameshift with a predicted alternate stop codon (p.I306Sfs*56). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. However, although loss of function of JUP is pathogenic with respect to autosomal recessive disease, loss of function has not been clearly established as a mechanism of disease for autosomal dominant arrhythmogenic right ventricular cardiomyopathy (AD ARVC). Since evidence supporting a role for this alteration in AD ARVC is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003103566	SCV003512410	pathogenic	Naxos disease; Arrhythmogenic right ventricular dysplasia 12	2022-09-29	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with JUP-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile306Serfs*56) in the JUP gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in JUP are known to be pathogenic (PMID: 10902626).