Submissions for variant NM_000214.3(JAG1):c.526G>A (p.Val176Ile)

gnomAD frequency: 0.00013  dbSNP: rs199674138

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000271780	SCV000432944	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.
Eurofins Ntd Llc (ga)	RCV000728706	SCV000856311	likely benign	not specified	2017-08-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000827896	SCV000969567	likely benign	not provided	2018-05-14	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001078642	SCV001005757	likely benign	Alagille syndrome due to a JAG1 point mutation	2023-12-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002348090	SCV002643386	likely benign	Cardiovascular phenotype	2018-07-13	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Fulgent Genetics, Fulgent Genetics	RCV002488725	SCV002797267	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	2022-04-03	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004549772	SCV004767826	likely benign	JAG1-related disorder	2021-06-23	no assertion criteria provided	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).