Submissions for variant NM_020433.5(JPH2):c.572C>G (p.Pro191Arg)

gnomAD frequency: 0.00048  dbSNP: rs554853074

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000786325	SCV000235927	likely benign	not provided	2021-09-24	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 30847666, 29874181)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000223019	SCV000271857	benign	not specified	2020-08-18	criteria provided, single submitter	clinical testing	The p.Pro191Arg variant in JPH2 is classified as benign because it has been identified in 0.7% (26/3474) of Ashkenazi Jewish chromosomes and in 0.05% (46/88966) of the total chromosomes by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BA1.
Ambry Genetics	RCV000253404	SCV000319687	benign	Cardiovascular phenotype	2015-06-18	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001086480	SCV000541247	benign	Hypertrophic cardiomyopathy	2024-01-22	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000223019	SCV000740572	likely benign	not specified	2017-04-11	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000786325	SCV004562272	likely benign	not provided	2023-10-19	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000786325	SCV004701377	benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	JPH2: BS1, BS2
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000223019	SCV005039480	benign	not specified	2024-03-12	criteria provided, single submitter	clinical testing	Variant summary: JPH2 c.572C>G (p.Pro191Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00069 in 58082 control chromosomes. The observed variant frequency is approximately 28 fold of the estimated maximal expected allele frequency for a pathogenic variant in JPH2 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.572C>G in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 201796). Based on the evidence outlined above, the variant was classified as benign.
Stanford Center for Inherited Cardiovascular Disease, Stanford University	RCV000786325	SCV000925100	uncertain significance	not provided	2016-03-10	no assertion criteria provided	provider interpretation
Clinical Genetics, Academic Medical Center	RCV000786325	SCV001919546	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000786325	SCV001927669	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000786325	SCV001956590	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000786325	SCV001975309	likely benign	not provided		no assertion criteria provided	clinical testing