Submissions for variant NM_002230.4(JUP):c.1982G>A (p.Arg661Gln)

gnomAD frequency: 0.00008  dbSNP: rs555499592

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079037	SCV000550397	likely benign	Naxos disease; Arrhythmogenic right ventricular dysplasia 12	2024-01-22	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000757415	SCV000885624	uncertain significance	not provided	2018-04-20	criteria provided, single submitter	clinical testing	The JUP c.1982G>A; p.Arg661Gln variant (rs555499592, ClinVar variant ID 409985), to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the genome Aggregation Database (gnomAD) with an overall population frequency of 0.1% (identified on 27 out of 18,870 chromosomes). The arginine at position 661 is moderately conserved, considering 13 species, and computational analyses of the effects of the p.Arg661Gln variant on protein structure and function do not predict a deleterious effect (SIFT: tolerated, PolyPhen-2: benign). Based on the available information, the clinical significance of the p.Arg661Gln variant cannot be determined with certainty.
Illumina Laboratory Services, Illumina	RCV001127665	SCV001287002	uncertain significance	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, 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.
Illumina Laboratory Services, Illumina	RCV001127666	SCV001287003	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.
GeneDx	RCV000757415	SCV002575876	uncertain significance	not provided	2022-09-19	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has been reported in association with dilated cardiomyopathy (Verdonschot et al., 2020); This variant is associated with the following publications: (PMID: 32880476)
Ambry Genetics	RCV002418404	SCV002722935	benign	Cardiovascular phenotype	2022-05-27	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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000757415	SCV001742391	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000757415	SCV001958095	uncertain significance	not provided		no assertion criteria provided	clinical testing