Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001880192 | SCV002158013 | uncertain significance | Alagille syndrome due to a JAG1 point mutation | 2023-03-26 | 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. 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 not expected to disrupt JAG1 protein function. ClinVar contains an entry for this variant (Variation ID: 988259). This variant has not been reported in the literature in individuals affected with JAG1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 108 of the JAG1 protein (p.Asn108Ile). |
| Fulgent Genetics, |
RCV002486020 | SCV002777864 | 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 | 2022-04-16 | criteria provided, single submitter | clinical testing | |
| Sydney Genome Diagnostics, |
RCV001328305 | SCV001449327 | uncertain significance | Congenital anomaly of kidney and urinary tract | 2020-01-20 | no assertion criteria provided | clinical testing | This individual is heterozygous for the c.323A>T variant in the JAG1 gene, which results in the amino acid substitution of asparagine to isoleucine at residue 108, p.(Asn108Ile). The variant has not been reported in any population databases (i.e. gnomAD, ExAC, ESP or dbSNP). To our knowledge, this variant has not been previously reported in the literature or any disease specific databases. In silico analysis of pathogenicity (through Alamut Visual v2.13) is inconclusive regarding this change; PolyPhen2 and MutationTaster predicts it to be likely pathogenic whereas SIFT predicts this variant to be benign. This variant is considered to be a variant of uncertain clinical significance (VOUS) according to the ACMG guidelines (Evidence used: PM2). |