Submissions for variant NM_000214.3(JAG1):c.2231G>A (p.Arg744Gln)

gnomAD frequency: 0.00069  dbSNP: rs147809756

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000262497	SCV000432907	benign	Isolated Nonsyndromic Congenital Heart Disease	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae	RCV000471378	SCV000557600	likely benign	Alagille syndrome due to a JAG1 point mutation	2024-01-29	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000595286	SCV000704671	likely benign	not specified	2017-01-13	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000620807	SCV000735310	likely benign	Cardiovascular phenotype	2018-02-22	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.
GeneDx	RCV001528251	SCV001939593	likely benign	not provided	2018-12-17	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 11139239, 10220506, 11157803, 11058898, 26760175)
Fulgent Genetics, Fulgent Genetics	RCV002504137	SCV002808883	likely benign	Alagille syndrome due to a JAG1 point mutation; Tetralogy of Fallot; Deafness, congenital heart defects, and posterior embryotoxon; Charcot-Marie-Tooth disease, axonal, Type 2HH	2022-04-11	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003972428	SCV004797552	likely benign	JAG1-related condition	2020-01-31	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528251	SCV001739668	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001528251	SCV001965329	uncertain significance	not provided		no assertion criteria provided	clinical testing