Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001061659 | SCV001226409 | uncertain significance | Adams-Oliver syndrome 5 | 2023-01-18 | 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 NOTCH1 protein function. ClinVar contains an entry for this variant (Variation ID: 856242). This variant has not been reported in the literature in individuals affected with NOTCH1-related conditions. This variant is present in population databases (rs367589813, gnomAD 0.001%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1523 of the NOTCH1 protein (p.Arg1523His). |
Gene |
RCV002282446 | SCV002571602 | uncertain significance | not provided | 2022-09-08 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31629061) |
Fulgent Genetics, |
RCV002505630 | SCV002816422 | uncertain significance | Aortic valve disease 1; Adams-Oliver syndrome 5 | 2021-10-04 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003346293 | SCV004074193 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-06-28 | criteria provided, single submitter | clinical testing | The p.R1523H variant (also known as c.4568G>A), located in coding exon 25 of the NOTCH1 gene, results from a G to A substitution at nucleotide position 4568. The arginine at codon 1523 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |