Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000255615 | SCV000321789 | pathogenic | not provided | 2016-04-20 | criteria provided, single submitter | clinical testing | The c.3048+1 G>A splice site variant in the JAG1 gene destroys the canonical splice donor site in intron 24. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The 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. |
Eurofins Ntd Llc |
RCV000255615 | SCV000709309 | pathogenic | not provided | 2017-06-12 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001859478 | SCV002116426 | uncertain significance | Alagille syndrome due to a JAG1 point mutation | 2022-04-28 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 24 of the JAG1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with Alagille syndrome (PMID: 15772854). ClinVar contains an entry for this variant (Variation ID: 265204). Studies have shown that disruption of this splice site results in skipping of exon 24, but is expected to preserve the integrity of the reading-frame (PMID: 15772854). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |