Submissions for variant NM_002230.4(JUP):c.1172G>A (p.Ser391Asn)

gnomAD frequency: 0.00016  dbSNP: rs199826380

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000171959	SCV000054835	uncertain significance	not provided	2013-06-24	criteria provided, single submitter	research
GeneDx	RCV000171959	SCV000235936	likely benign	not provided	2019-05-06	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001085221	SCV000645721	likely benign	Naxos disease; Arrhythmogenic right ventricular dysplasia 12	2024-01-27	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000171959	SCV000699460	benign	not provided	2016-05-09	criteria provided, single submitter	clinical testing	Variant summary: The JUP c.1172G>A (p.Ser391Asn) variant involves the alteration of a non-conserved nucleotide. 3/3 in silico tools predict a benign outcome for this variant. This variant was found in 29/122542 control chromosomes at a frequency of 0.0002367, which is approximately 24 times the estimated maximal expected allele frequency of a pathogenic JUP variant (0.00001), suggesting this variant is likely a benign polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. It has been classified as a likely benign by one clinical laboratory in ClinVar. One internal sample carrying this variant also carried a potentially pathogenic variant SCN5A c.5350G>A (p.E1784K) (classified as pathogenic by multiple labs and databases in ClinVar), further supporting the benign outcome. Taken together, this variant is classified as Benign.
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852719	SCV000995433	likely benign	Cardiomyopathy	2018-05-23	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001124754	SCV001283741	uncertain significance	Naxos disease	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001125740	SCV001284842	uncertain significance	Arrhythmogenic right ventricular dysplasia 12	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Ambry Genetics	RCV002326943	SCV002633096	likely benign	Cardiovascular phenotype	2019-09-16	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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV001085221	SCV003920086	uncertain significance	Naxos disease; Arrhythmogenic right ventricular dysplasia 12	2021-03-30	criteria provided, single submitter	clinical testing	JUP NM_002230.2 exon 8 p.Ser391Asn (c.1172G>A): This variant has not been reported in the literature but is present in 0.2% (27/10354) of Ashkenazi Jewish alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/17-39919560-C-T). This variant is present in ClinVar (Variation ID:191672). This variant amino acid Asparagine (Asn) is present in 4 species and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Clinical Genetics, Academic Medical Center	RCV001706115	SCV001920436	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000171959	SCV001975102	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003954999	SCV004774994	likely benign	JUP-related disorder	2023-08-31	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).