Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001343536 | SCV001537524 | uncertain significance | Alagille syndrome due to a JAG1 point mutation | 2020-06-13 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with JAG1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with serine at codon 29 of the JAG1 protein (p.Cys29Ser). The cysteine residue is moderately conserved and there is a moderate physicochemical difference between cysteine and serine. |
| Fulgent Genetics, |
RCV002486395 | SCV002783396 | 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 | 2022-03-02 | criteria provided, single submitter | clinical testing |