Submissions for variant NM_020433.5(JPH2):c.637C>T (p.Arg213Trp)

gnomAD frequency: 0.00145  dbSNP: rs767328866

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001721140	SCV000235928	likely benign	not provided	2021-05-14	criteria provided, single submitter	clinical testing
Invitae	RCV000200580	SCV000255038	benign	Hypertrophic cardiomyopathy	2024-01-18	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000183468	SCV000271858	uncertain significance	not specified	2015-06-12	criteria provided, single submitter	clinical testing	The p.Arg213Trp variant in JPH2 has not been previously reported in individuals with cardiomyopathy, but has been identified in 0.1% (4/3380) of South Asian chr omosomes and 1/82 African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Computational prediction tools and conservatio n analysis do not provide strong support for or against an impact to the protein . In summary, the clinical significance of the p.Arg213Trp variant is uncertain.
Ambry Genetics	RCV000618873	SCV000735160	likely benign	Cardiovascular phenotype	2019-11-21	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001721140	SCV003800469	likely benign	not provided	2023-10-10	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224202	SCV003920079	uncertain significance	Hypertrophic cardiomyopathy 17; Cardiomyopathy, dilated, 2E	2021-03-30	criteria provided, single submitter	clinical testing	JPH2 NM_020433.4 exon 2 p.Arg213Trp (c.637C>T): This variant has not been reported in the literature but is present in 0.07% (64/81352) of total alleles in the Genome Aggregation Database, including 2 homozygotes (https://gnomad.broadinstitute.org/variant/20-42788790-G-A). This variant is present in ClinVar (Variation ID:201797). Evolutionary conservation and computational predictive tools for this variant are unclear. 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	RCV000183468	SCV001921975	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001721140	SCV001967620	likely benign	not provided		no assertion criteria provided	clinical testing