Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002357950 | SCV002660034 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2024-12-28 | criteria provided, single submitter | clinical testing | The p.A340T variant (also known as c.1018G>A), located in coding exon 6 of the NOTCH1 gene, results from a G to A substitution at nucleotide position 1018. The alanine at codon 340 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003098096 | SCV002978338 | uncertain significance | Adams-Oliver syndrome 5 | 2021-11-29 | 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 affected with NOTCH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 340 of the NOTCH1 protein (p.Ala340Thr). |