Submissions for variant NM_002230.4(JUP):c.406G>C (p.Asp136His)

dbSNP: rs782392706

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000183484	SCV000235944	likely pathogenic	not provided	2013-11-20	criteria provided, single submitter	clinical testing	p.Asp136His (GAT>CAT): c.406 G>C in exon 3 of the JUP gene (NM_002230.2). The Asp136His variant in the JUP gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Asp136His results in a non-conservative amino acid substitution of a negatively charged Aspartic acid to a positively charged Histidine at a position that is conserved across species. In silico analysis predicts Asp136His is probably damaging to the protein structure/function. Furthermore, the Asp136His variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The variant is found in ARRHYTHMIA panel(s).
Labcorp Genetics (formerly Invitae), Labcorp	RCV001056315	SCV001220753	uncertain significance	Naxos disease; Arrhythmogenic right ventricular dysplasia 12	2023-07-03	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. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 201810). This variant has not been reported in the literature in individuals affected with JUP-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 136 of the JUP protein (p.Asp136His).
Ambry Genetics	RCV004020217	SCV005018397	uncertain significance	Cardiovascular phenotype	2024-01-11	criteria provided, single submitter	clinical testing	The p.D136H variant (also known as c.406G>C), located in coding exon 2 of the JUP gene, results from a G to C substitution at nucleotide position 406. The aspartic acid at codon 136 is replaced by histidine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.