Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001962848 | SCV002212622 | uncertain significance | Hajdu-Cheney syndrome | 2023-07-07 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs760325217, gnomAD 0.004%). 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 NOTCH2 protein function. ClinVar contains an entry for this variant (Variation ID: 1437501). This variant has not been reported in the literature in individuals affected with NOTCH2-related conditions. This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1424 of the NOTCH2 protein (p.Thr1424Ala). |
| Fulgent Genetics, |
RCV002479512 | SCV002785077 | uncertain significance | Alagille syndrome due to a NOTCH2 point mutation; Hajdu-Cheney syndrome | 2021-12-27 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003303459 | SCV004005755 | uncertain significance | Inborn genetic diseases | 2023-04-07 | criteria provided, single submitter | clinical testing | The c.4270A>G (p.T1424A) alteration is located in exon 25 (coding exon 25) of the NOTCH2 gene. This alteration results from a A to G substitution at nucleotide position 4270, causing the threonine (T) at amino acid position 1424 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |