ClinVar Miner

Submissions for variant NM_000214.3(JAG1):c.3164_3167del (p.Val1055fs)

dbSNP: rs1555827653
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000726702 SCV000702206 pathogenic not provided 2017-04-24 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000594760 SCV000831758 pathogenic Alagille syndrome due to a JAG1 point mutation 2018-01-11 criteria provided, single submitter clinical testing Other truncating variants downstream of p.Val1055Glufs*7 have been reported to be de novo in Allagile syndrome cases (PMID: 26076142). This suggests that deletion of this region of the JAG1 protein is causative of disease. For these reasons, this variant has been classified as Pathogenic. This variant results in the deletion of the entire transmembrane domain of the JAG1 protein and should render it unable to attach to the cytoplasmic membrane (PMID: 26548814). This variant has been reported in individuals affected with Alagille syndrome, being found to be de novo in one case (PMID: 25676721, 10220506). This variant is also known as 3577–3580delTAAG in the literature. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the JAG1 gene (p.Val1055Glufs*7). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 164 amino acids of the JAG1 protein.
GeneDx RCV000726702 SCV003845497 pathogenic not provided 2023-03-01 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation, as the last 164 amino acids are replaced with 6 different amino acids, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31160058, 32369273, 17949281, 11139247, 10220506, 31343788, 29555955, 25676721)
OMIM RCV000594760 SCV002102477 pathogenic Alagille syndrome due to a JAG1 point mutation 2022-03-02 no assertion criteria provided literature only

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