Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000792631 | SCV000931937 | pathogenic | Alagille syndrome due to a JAG1 point mutation | 2018-10-06 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in JAG1 are known to be pathogenic (PMID: 11180599). This variant has been observed in an individual affected with Alagille syndrome (PMID: 11180599). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu353*) in the JAG1 gene. It is expected to result in an absent or disrupted protein product. |
Ambry Genetics | RCV002397567 | SCV002713255 | pathogenic | Cardiovascular phenotype | 2016-05-12 | criteria provided, single submitter | clinical testing | The p.E353* pathogenic mutation (also known as c.1057G>T), located in coding exon 8 of the JAG1 gene, results from a G to T substitution at nucleotide position 1057. This changes the amino acid from a glutamic acid to a stop codon within coding exon 8. This mutation has been described in a patient with a clinical diagnosis of Alagille syndrome (Colliton RP, Hum. Mutat. 2001 Feb; 17(2):151-2). In addition to the clinical data presented in the literature, since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). |