Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002315102 | SCV000739455 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2016-12-02 | criteria provided, single submitter | clinical testing | The p.G2345S variant (also known as c.7033G>A), located in coding exon 34 of the NOTCH1 gene, results from a G to A substitution at nucleotide position 7033. The glycine at codon 2345 is replaced by serine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and serine is the reference amino acid in other vertebrate species. 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. |
Gene |
RCV001591391 | SCV001826799 | uncertain significance | not provided | 2021-01-15 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Reported in ClinVar as a variant of uncertain significance, but additional evidence is not available (ClinVar Variant ID# 520058; Landrum et al., 2016) |
Genome- |
RCV002270898 | SCV002553264 | uncertain significance | Adams-Oliver syndrome 5 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV002270897 | SCV002553265 | uncertain significance | Aortic valve disease 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002270898 | SCV004382866 | uncertain significance | Adams-Oliver syndrome 5 | 2025-01-26 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2345 of the NOTCH1 protein (p.Gly2345Ser). This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with NOTCH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 520058). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt NOTCH1 protein function with a negative predictive value of 80%. 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. |