Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000655227 | SCV000777157 | uncertain significance | Adams-Oliver syndrome 5 | 2021-10-16 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with leucine at codon 879 of the NOTCH1 protein (p.Arg879Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with NOTCH1-related conditions. This variant is present in population databases (rs368011392, ExAC 0.002%). |
| Ambry Genetics | RCV002424554 | SCV002741275 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-03-08 | criteria provided, single submitter | clinical testing | The p.R879L variant (also known as c.2636G>T), located in coding exon 17 of the NOTCH1 gene, results from a G to T substitution at nucleotide position 2636. The arginine at codon 879 is replaced by leucine, an amino acid with dissimilar 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. |