ClinVar Miner

Submissions for variant NM_000214.3(JAG1):c.2091_2095GAAAG[1] (p.Gly699fs) (rs886039393)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255046 SCV000321788 pathogenic not provided 2016-06-21 criteria provided, single submitter clinical testing The c.2096_2100delGAAAG pathogenic variant in the JAG1 gene has been reported previously in two unrelated individuals with Alagille syndrome using alternate nomenclature c.2504del5 (Krantz et al., 1998). The c.2096_2100delGAAAG variant causes a frameshift starting with codon Glycine 699, changes this amino acid to an Aspartic Acid residue, and creates a premature Stop codon at position 6 of the new reading frame, denoted p.Gly699AspfsX6. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.2096_2100delGAAAG variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.2096_2100delGAAAG as a pathogenic variant.
Invitae RCV000008060 SCV000645524 pathogenic Alagille syndrome 1 2017-03-22 criteria provided, single submitter clinical testing This sequence change deletes 5 nucleotides from exon 16 of the JAG1 mRNA (c.2096_2100delGAAAG), causing a frameshift at codon 699. This creates a premature translational stop signal (p.Gly699Aspfs*6) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in JAG1 are known to be pathogenic. This particular variant has been reported in the literature in individuals affected with Alagille syndrome (PMID: 9585603). It is also called 2504del5 in the literature. For these reasons, this variant has been classified as Pathogenic.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000255046 SCV000708478 pathogenic not provided 2018-09-12 criteria provided, single submitter clinical testing
OMIM RCV000008060 SCV000028265 pathogenic Alagille syndrome 1 1998-06-01 no assertion criteria provided literature only

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