ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.562G>A (p.Ala188Thr)

gnomAD frequency: 0.00001  dbSNP: rs782585387
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000645209 SCV000766951 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2023-06-24 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 188 of the JUP protein (p.Ala188Thr). 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 missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 31983221). ClinVar contains an entry for this variant (Variation ID: 536632). 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001798945 SCV002043158 uncertain significance Cardiomyopathy 2020-04-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV002343314 SCV002654217 uncertain significance Cardiovascular phenotype 2022-08-17 criteria provided, single submitter clinical testing The p.A188T variant (also known as c.562G>A), located in coding exon 3 of the JUP gene, results from a G to A substitution at nucleotide position 562. The alanine at codon 188 is replaced by threonine, an amino acid with similar properties. This alteration has been reported in a dilated cardiomyopathy (DCM) cohort (Mazzarotto F et al. Circulation, 2020 02;141:387-398). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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