Submissions for variant NM_020433.5(JPH2):c.1714C>T (p.Arg572Cys)

dbSNP: rs377366285

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000519704	SCV000618741	uncertain significance	not provided	2020-04-14	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Labcorp Genetics (formerly Invitae), Labcorp	RCV001219746	SCV001391699	uncertain significance	Hypertrophic cardiomyopathy	2024-09-16	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 572 of the JPH2 protein (p.Arg572Cys). 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 variant has not been reported in the literature in individuals affected with JPH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 450190). 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. 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.
Ambry Genetics	RCV002404344	SCV002712307	uncertain significance	Cardiovascular phenotype	2023-04-03	criteria provided, single submitter	clinical testing	The p.R572C variant (also known as c.1714C>T), located in coding exon 4 of the JPH2 gene, results from a C to T substitution at nucleotide position 1714. The arginine at codon 572 is replaced by cysteine, an amino acid with highly dissimilar properties. 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224306	SCV003920076	uncertain significance	Hypertrophic cardiomyopathy 17; Cardiomyopathy, dilated, 2E		criteria provided, single submitter	clinical testing	JPH2 NM_020433.4 exon 4 p.Arg572Cys (c.1714C>T): This variant has not been reported in the literature and is present in 0.01% (9/75564) of European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/20-42744601-G-A). This variant is present in ClinVar (Variation ID:450190). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Clinical Genetics, Academic Medical Center	RCV000519704	SCV001924615	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000519704	SCV001958251	uncertain significance	not provided		no assertion criteria provided	clinical testing