Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000231293 | SCV000290257 | uncertain significance | Adams-Oliver syndrome 5 | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with alanine at codon 915 of the NOTCH1 protein (p.Pro915Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with NOTCH1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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 | RCV003278714 | SCV003960912 | uncertain significance | Inborn genetic diseases | 2023-04-17 | criteria provided, single submitter | clinical testing | The c.2743C>G (p.P915A) alteration is located in exon 18 (coding exon 18) of the NOTCH1 gene. This alteration results from a C to G substitution at nucleotide position 2743, causing the proline (P) at amino acid position 915 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |