Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000228959 | SCV000290308 | uncertain significance | Adams-Oliver syndrome 5 | 2016-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with serine at codon 2427 of the NOTCH1 protein (p.Gly2427Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs370722609, ExAC 0.01%) but has not been reported in the literature in individuals with a NOTCH1-related disease. The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. In addition, 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 tolerated, but these predictions have not been confirmed by published functional studies. In summary, this is a rare missense change with uncertain impact on protein function. There is no indication that this variant causes disease, but the evidence is insufficient at this time to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Blueprint Genetics | RCV000788485 | SCV000927621 | uncertain significance | not provided | 2018-04-09 | criteria provided, single submitter | clinical testing |