Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003081153 | SCV003456482 | uncertain significance | Adams-Oliver syndrome 5 | 2023-07-10 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1507 of the NOTCH1 protein (p.Ser1507Asn). 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. ClinVar contains an entry for this variant (Variation ID: 2148457). 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). |
| Ambry Genetics | RCV004070464 | SCV004990175 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2024-02-05 | criteria provided, single submitter | clinical testing | The c.4520G>A (p.S1507N) alteration is located in exon 25 (coding exon 25) of the NOTCH1 gene. This alteration results from a G to A substitution at nucleotide position 4520, causing the serine (S) at amino acid position 1507 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |