ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.1787C>T (p.Ser596Leu)

gnomAD frequency: 0.00001  dbSNP: rs940226194
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000692165 SCV000819975 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2022-03-18 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 571117). This missense change has been observed in individual(s) with clinical features of dilated cardiomyopathy (PMID: 31983221). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 596 of the JUP protein (p.Ser596Leu).
Ambry Genetics RCV002397399 SCV002714407 uncertain significance Cardiovascular phenotype 2021-04-16 criteria provided, single submitter clinical testing The p.S596L variant (also known as c.1787C>T), located in coding exon 10 of the JUP gene, results from a C to T substitution at nucleotide position 1787. The serine at codon 596 is replaced by leucine, an amino acid with dissimilar properties. This variant was reported in one individual from a dilated cardiomyopathy (DCM) cohort with limited clinical details provided (Mazzarotto F et al. Circulation, 2020 02;141:387-398). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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