Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002302312 | SCV002592674 | uncertain significance | Alagille syndrome due to a JAG1 point mutation | 2022-10-21 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt JAG1 protein function. This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 757 of the JAG1 protein (p.Gly757Asp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with JAG1-related conditions. |
Fulgent Genetics, |
RCV005025782 | SCV005656296 | uncertain significance | Alagille syndrome due to a JAG1 point mutation; Tetralogy of Fallot; Deafness, congenital heart defects, and posterior embryotoxon; Charcot-Marie-Tooth disease, axonal, Type 2HH | 2024-06-04 | criteria provided, single submitter | clinical testing |