ClinVar Miner

Submissions for variant NM_000214.3(JAG1):c.860A>G (p.Asn287Ser)

gnomAD frequency: 0.00001  dbSNP: rs768317581
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000213865 SCV000279440 uncertain significance not provided 2015-09-20 criteria provided, single submitter clinical testing The N287S variant in the JAG1 gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The N287S variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The N287S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (C284F, W288C) have been reported in the Human Gene Mutation Database in association with Alagille syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, we interpret N287S as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001369966 SCV001566425 likely benign Alagille syndrome due to a JAG1 point mutation 2022-12-25 criteria provided, single submitter clinical testing
Ambry Genetics RCV002444870 SCV002681410 uncertain significance Cardiovascular phenotype 2022-09-17 criteria provided, single submitter clinical testing The p.N287S variant (also known as c.860A>G), located in coding exon 6 of the JAG1 gene, results from an A to G substitution at nucleotide position 860. The asparagine at codon 287 is replaced by serine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002485440 SCV002776123 uncertain significance 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 2021-12-01 criteria provided, single submitter clinical testing

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