Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Centre of Medical Genetics, |
RCV000662256 | SCV000747177 | uncertain significance | Adams-Oliver syndrome 5 | 2017-12-01 | criteria provided, single submitter | research | |
Invitae | RCV000662256 | SCV004461122 | uncertain significance | Adams-Oliver syndrome 5 | 2023-04-29 | 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 expected to disrupt NOTCH1 protein function. ClinVar contains an entry for this variant (Variation ID: 523602). This missense change has been observed in individual(s) with Adams–Oliver syndrome (PMID: 29924900). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 2034 of the NOTCH1 protein (p.Trp2034Arg). |