Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Centre of Medical Genetics, |
RCV000662252 | SCV000747173 | likely pathogenic | Adams-Oliver syndrome 5 | 2017-12-01 | criteria provided, single submitter | research | |
Gene |
RCV003223659 | SCV003919493 | likely pathogenic | not provided | 2022-10-20 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28191890, 28991257, 32368696, 26785492, 29924900) |
Invitae | RCV000662252 | SCV004295622 | pathogenic | Adams-Oliver syndrome 5 | 2024-01-13 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1517 of the NOTCH1 protein (p.Asp1517Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Adams–Oliver syndrome and/or congenital heart disease (PMID: 12774039, 26785492, 29924900, 31941532). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 523598). 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 with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |