Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000655239 | SCV000777169 | uncertain significance | Adams-Oliver syndrome 5 | 2022-10-03 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 544169). This variant has not been reported in the literature in individuals affected with NOTCH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 2115 of the NOTCH1 protein (p.Glu2115Lys). |
| Ambry Genetics | RCV004649256 | SCV005142118 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2024-04-07 | criteria provided, single submitter | clinical testing | The p.E2115K variant (also known as c.6343G>A), located in coding exon 34 of the NOTCH1 gene, results from a G to A substitution at nucleotide position 6343. The glutamic acid at codon 2115 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |