ClinVar Miner

Submissions for variant NM_000214.3(JAG1):c.2666G>A (p.Arg889Gln)

gnomAD frequency: 0.00011  dbSNP: rs149419694
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000220286 SCV000278992 uncertain significance not provided 2016-01-06 criteria provided, single submitter clinical testing The R889Q variant of uncertain significance has been published previously in association with Alagille syndrome (Warthen et al., 2006). The variant was not observed at any significant frequency 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. R889Q is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position where amino acids with similar properties to Arginine are tolerated across species; however, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV000476409 SCV000545808 likely benign Alagille syndrome due to a JAG1 point mutation 2023-12-04 criteria provided, single submitter clinical testing
SIB Swiss Institute of Bioinformatics RCV000476409 SCV000803513 uncertain significance Alagille syndrome due to a JAG1 point mutation 2018-05-31 criteria provided, single submitter curation This variant is interpreted as a Uncertain Significance - Insufficient Evidence, for Alagille syndrome 1, in Autosomal Dominant manner. The following ACMG Tag(s) were applied: BS1 => Allele frequency is greater than expected for disorder.
Fulgent Genetics, Fulgent Genetics RCV000765486 SCV000896781 uncertain significance Alagille syndrome due to a JAG1 point mutation; Tetralogy of Fallot; Deafness, congenital heart defects, and posterior embryotoxon 2018-10-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV002429080 SCV002743841 uncertain significance Cardiovascular phenotype 2018-11-26 criteria provided, single submitter clinical testing The p.R889Q variant (also known as c.2666G>A), located in coding exon 22 of the JAG1 gene, results from a G to A substitution at nucleotide position 2666. The arginine at codon 889 is replaced by glutamine, an amino acid with highly similar properties. This variant was identified in a cohort of individuals with Alagille syndrome; however, additional clinical details were not provided (Warthen DM et al. Hum. Mutat., 2006 May;27:436-43). This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on available evidence to date, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV000220286 SCV003813889 uncertain significance not provided 2023-02-01 criteria provided, single submitter clinical testing

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