Submissions for variant NM_000214.3(JAG1):c.2429C>T (p.Pro810Leu)

gnomAD frequency: 0.00001  dbSNP: rs769531968

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000626071	SCV000746695	pathogenic	Alagille syndrome due to a JAG1 point mutation	2017-12-18	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000730482	SCV000858220	uncertain significance	not provided	2017-12-05	criteria provided, single submitter	clinical testing
SIB Swiss Institute of Bioinformatics	RCV000755708	SCV000883167	likely pathogenic	Tetralogy of Fallot	2018-10-15	criteria provided, single submitter	curation	This variant is interpreted as Likely Pathogenic, for Tetralogy of Fallot. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PS3 => Well-established functional studies show a deleterious effect (https://www.ncbi.nlm.nih.gov/pubmed/20437614).
GeneDx	RCV000730482	SCV001822879	uncertain significance	not provided	2023-06-28	criteria provided, single submitter	clinical testing	Identified in patients with clinical features that include tetralogy of Fallot, cleft lip and palate, and mild intellectual disability, in an individual with an atrioventricular septal defect, and in an individual with a rare lymphatic anomaly with pulmonary artery stenosis and dysmorphic facial features in published literature (Alankarage et al., 2019; Li et al., 2021; Bauer et al., 2010; Guida et al., 2011; Alankarage et al., 2019; Li et al., 2021); One published functional study suggests a damaging effect; however additional studies are needed to validate the functional effect of this variant (Bauer et al., 2010); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22040217, 31813956, 33433009, 30293987, 34358384, 20437614)
AiLife Diagnostics, AiLife Diagnostics	RCV000730482	SCV002501989	uncertain significance	not provided	2022-02-13	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000626071	SCV004476038	likely benign	Alagille syndrome due to a JAG1 point mutation	2023-12-27	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000626071	SCV004806801	uncertain significance	Alagille syndrome due to a JAG1 point mutation	2024-03-26	criteria provided, single submitter	clinical testing