Submissions for variant NM_002230.4(JUP):c.426C>T (p.Arg142=)

gnomAD frequency: 0.00018  dbSNP: rs142599474

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000546497	SCV000645731	benign	Naxos disease; Arrhythmogenic right ventricular dysplasia 12	2024-01-25	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001193380	SCV001362161	benign	not specified	2019-10-30	criteria provided, single submitter	clinical testing	Variant summary: JUP c.426C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00016 in 246898 control chromosomes. The observed variant frequency is approximately 6.48 fold of the estimated maximal expected allele frequency for a pathogenic variant in JUP causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.426C>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
GeneDx	RCV001653905	SCV001865588	likely benign	not provided	2021-06-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002330913	SCV002631704	likely benign	Cardiovascular phenotype	2019-02-27	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001653905	SCV001927628	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001653905	SCV001955544	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001653905	SCV001964239	likely benign	not provided		no assertion criteria provided	clinical testing