Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001919183 | SCV002180539 | uncertain significance | Adams-Oliver syndrome 5 | 2021-02-15 | 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. This variant has not been reported in the literature in individuals with NOTCH1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with lysine at codon 2396 of the NOTCH1 protein (p.Asn2396Lys). The asparagine residue is weakly conserved and there is a moderate physicochemical difference between asparagine and lysine. |
| Ambry Genetics | RCV003167155 | SCV003861525 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-12-25 | criteria provided, single submitter | clinical testing | The p.N2396K variant (also known as c.7188C>G), located in coding exon 34 of the NOTCH1 gene, results from a C to G substitution at nucleotide position 7188. The asparagine at codon 2396 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |