ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.1172G>A (p.Ser391Asn) (rs199826380)

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Total submissions: 4
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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 uncertain significance not provided 2017-01-20 criteria provided, single submitter clinical testing The S391N variant has not been published as a pathogenic variant or been reported as a benign variant to our knowledge. This variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project or in the 1000 Genomes Project. Nevertheless, the S391N variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, this substitution occurs at a position where Asparagine is tolerated in several other species. Consequently, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Furthermore, no missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with ARVC (Stenson et al., 2014), indicating that this region of the gene is not known to harbor disease-causing variants. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.
Integrated Genetics/Laboratory Corporation of America 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.
Invitae RCV000527518 SCV000645721 likely benign Naxos disease; Arrhythmogenic right ventricular cardiomyopathy, type 12 2017-12-18 criteria provided, single submitter clinical testing

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