Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000461377 | SCV000548955 | uncertain significance | Adams-Oliver syndrome 5 | 2017-03-21 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a NOTCH1-related disease. This sequence change replaces alanine with aspartic acid at codon 1325 of the NOTCH1 protein (p.Ala1325Asp). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and aspartic acid. 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, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. |
| Gene |
RCV001770342 | SCV002002741 | uncertain significance | not provided | 2021-03-29 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 409072; Landrum et al., 2016) |
| Genome- |
RCV000461377 | SCV002553456 | uncertain significance | Adams-Oliver syndrome 5 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Genome- |
RCV002270505 | SCV002553457 | uncertain significance | Aortic valve disease 1 | 2022-03-15 | criteria provided, single submitter | clinical testing |