ClinVar Miner

Submissions for variant NM_000214.3(JAG1):c.439+1G>A

dbSNP: rs863223648
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000199991 SCV000250455 pathogenic not provided 2015-05-12 criteria provided, single submitter clinical testing The c.439+1 G>A splice site mutation in the JAG1 gene has been previously reported in association with Alagille syndrome (Crosnier et al., 2001; Jurkiewicz et al. 2014). This mutation destroys the canonical splice donor site in intron 3, and is expected to cause abnormal gene splicing.This mutation destroys the canonical splice donor site in intron 3, and is expected to cause abnormal gene splicing. This variant was found in JAG1-T1
Eurofins Ntd Llc (ga) RCV000199991 SCV000707317 pathogenic not provided 2017-03-23 criteria provided, single submitter clinical testing
Invitae RCV001853157 SCV002242883 pathogenic Alagille syndrome due to a JAG1 point mutation 2023-11-20 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 3 of the JAG1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in JAG1 are known to be pathogenic (PMID: 11180599). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with Alagille syndrome (PMID: 11139247, 11180599, 29483232, 31343788). ClinVar contains an entry for this variant (Variation ID: 213529). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences RCV003417708 SCV004117208 pathogenic JAG1-related condition 2024-02-09 criteria provided, single submitter clinical testing The JAG1 c.439+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant has been reported in multiple individuals with Alagille syndrome (Table 1, Crosnier et al. 2000. PubMed ID: 11139247; Table 1, Jurkiewicz et al. 2014. PubMed ID: 24748328; Ohashi et al. 2017. PubMed ID: 28695677), as well as an individual with midaortic syndrome (Table 1, Warejko et al. 2018. PubMed ID: 29483232). This variant has not been reported in a large population database, indicating this variant is rare. Variants that disrupt the consensus splice donor site in JAG1 are expected to be pathogenic. This variant is interpreted as pathogenic.
Yale Center for Mendelian Genomics, Yale University RCV000845195 SCV000987131 likely pathogenic Atypical coarctation of aorta 2018-02-26 no assertion criteria provided literature only

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