Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV005136858 | SCV005768451 | uncertain significance | Adams-Oliver syndrome 5 | 2025-01-07 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1603 of the NOTCH1 protein (p.Asn1603Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NOTCH1-related conditions. 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. |
| Ambry Genetics | RCV005379737 | SCV006039518 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2025-01-04 | criteria provided, single submitter | clinical testing | The p.N1603S variant (also known as c.4808A>G), located in coding exon 26 of the NOTCH1 gene, results from an A to G substitution at nucleotide position 4808. The asparagine at codon 1603 is replaced by serine, 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. Based on the available evidence, the clinical significance of this variant remains unclear. |