Submissions for variant NM_000214.3(JAG1):c.1395+3A>G

dbSNP: rs886044220

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000320018	SCV000343984	pathogenic	not provided	2016-07-18	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001218520	SCV001390405	pathogenic	Alagille syndrome due to a JAG1 point mutation	2023-11-07	criteria provided, single submitter	clinical testing	This sequence change falls in intron 11 of the JAG1 gene. It does not directly change the encoded amino acid sequence of the JAG1 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with Alagille syndrome (PMID: 10220506, 11058898, 24748328). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This variant is also known as c.1808+3A>G. ClinVar contains an entry for this variant (Variation ID: 289599). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in aberrant splicing of exon 11 and introduces a premature termination codon (PMID: 11058898). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV004021282	SCV005016496	pathogenic	Tetralogy of Fallot	2023-11-02	criteria provided, single submitter	clinical testing
Genomics And Bioinformatics Analysis Resource, Columbia University	RCV001218520	SCV004024092	likely pathogenic	Alagille syndrome due to a JAG1 point mutation		no assertion criteria provided	research