Submissions for variant NM_002230.4(JUP):c.777C>T (p.Gly259=)

gnomAD frequency: 0.00507  dbSNP: rs34890640

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039088	SCV000062766	benign	not specified	2012-09-14	criteria provided, single submitter	clinical testing	Gly259Gly in Exon 05 of JUP: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue, is not located within t he splice consensus sequence and has been identified in 1.7% (63/3738) of Africa n American chromosomes from a broad population by the NHLBI Exome Sequencing Pro ject (http://evs.gs.washington.edu/EVS; dbSNP rs34890640).
GeneDx	RCV000039088	SCV000168906	benign	not specified	2014-01-27	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001081340	SCV000560957	benign	Naxos disease; Arrhythmogenic right ventricular dysplasia 12	2024-01-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589047	SCV000699469	benign	not provided	2016-09-05	criteria provided, single submitter	clinical testing	Variant summary: The JUP c.777C>T (p.Gly259Gly) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 184/121102 control chromosomes (5 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.0167598 (174/10382). This frequency is about 1676 times the estimated maximal expected allele frequency of a pathogenic JUP variant (0.00001), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories have classified this variant as benign. The variant of interest has been reported in one sample with carcinoma of large intestine as a somatic occurrence without strong evidence for pathogenicity (COSMIC). Taken together, this variant is classified as Benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000589047	SCV000885626	benign	not provided	2022-09-13	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769495	SCV000900890	benign	Cardiomyopathy	2016-06-17	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001122072	SCV001280752	likely benign	Arrhythmogenic right ventricular dysplasia 12	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001122073	SCV001280753	uncertain significance	Naxos disease	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Clinical Genetics, Academic Medical Center	RCV000039088	SCV001919681	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000039088	SCV001952964	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000039088	SCV001964958	benign	not specified		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003974894	SCV004789965	benign	JUP-related disorder	2019-09-13	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).