ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.2179G>A (p.Asp727Asn)

gnomAD frequency: 0.00001  dbSNP: rs1285789744
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000618552 SCV000735847 uncertain significance Cardiovascular phenotype 2017-04-21 criteria provided, single submitter clinical testing The p.D727N variant (also known as c.2179G>A), located in coding exon 13 of the JUP gene, results from a G to A substitution at nucleotide position 2179. The aspartic acid at codon 727 is replaced by asparagine, an amino acid with highly similar properties. This alteration has been reported in a hypertrophic cardiomyopathy (HCM) cohort; however, clinical details were limited (Lopes LR et al. Heart, 2015 Feb;101:294-301). This amino acid position is highly 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.
Invitae RCV000645202 SCV000766944 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2023-11-01 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 727 of the JUP protein (p.Asp727Asn). This variant is present in population databases (no rsID available, gnomAD 0.02%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 25351510). ClinVar contains an entry for this variant (Variation ID: 518649). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
GeneDx RCV001584431 SCV001813006 likely benign not provided 2020-12-29 criteria provided, single submitter clinical testing Reported as a variant of uncertain significance by two other clinical laboratories in ClinVar but additional evidence is not available (ClinVar Variant ID# 518649; Landrum et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Identified in one individual with hypertrophic cardiomyopathy (HCM); however, detailed clinical information was not provided (Lopes et al., 2015); This variant is associated with the following publications: (PMID: 25351510)

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