Submissions for variant NM_000214.3(JAG1):c.1826C>T (p.Ser609Leu)

gnomAD frequency: 0.00009  dbSNP: rs199505265

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000197189	SCV000250462	uncertain significance	not provided	2024-10-29	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Illumina Laboratory Services, Illumina	RCV000351515	SCV000432917	benign	Isolated Nonsyndromic Congenital Heart Disease	2018-01-12	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)	RCV000197189	SCV000709272	uncertain significance	not provided	2017-06-09	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001062019	SCV001226788	likely benign	Alagille syndrome due to a JAG1 point mutation	2024-08-05	criteria provided, single submitter	clinical testing
Mendelics	RCV002247622	SCV002517215	uncertain significance	not specified	2022-05-04	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000197189	SCV003813883	uncertain significance	not provided	2019-11-11	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004553067	SCV004775800	uncertain significance	JAG1-related disorder	2024-01-16	no assertion criteria provided	clinical testing	The JAG1 c.1826C>T variant is predicted to result in the amino acid substitution p.Ser609Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.014% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.