Submissions for variant NM_020433.5(JPH2):c.1655C>T (p.Pro552Leu)

dbSNP: rs876657833

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000214728	SCV000271852	uncertain significance	not specified	2016-01-26	criteria provided, single submitter	clinical testing	The p.Pro552Leu variant in JPH2 has not been previously reported in individuals with cardiomyopathy and data from large population studies is insufficient to as sess the frequency of this variant. Computational prediction tools and conservat ion analysis do not provide strong support for or against an impact to the prote in. In summary, the clinical significance of the p.Pro552Leu variant is uncertai n.
GeneDx	RCV001753643	SCV001997079	uncertain significance	not provided	2019-12-24	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance by another clinical laboratory (ClinVar Variant ID# 228752; Landrum et al., 2016); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function
Ambry Genetics	RCV002390580	SCV002703521	uncertain significance	Cardiovascular phenotype	2022-03-23	criteria provided, single submitter	clinical testing	The p.P552L variant (also known as c.1655C>T), located in coding exon 4 of the JPH2 gene, results from a C to T substitution at nucleotide position 1655. The proline at codon 552 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. 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.