Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000466090 | SCV000548947 | uncertain significance | Adams-Oliver syndrome 5 | 2018-04-03 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with glutamine at codon 176 of the NOTCH1 protein (p.Arg176Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs375065108, ExAC 0.02%). This variant has not been reported in the literature in individuals with NOTCH1-related disease. ClinVar contains an entry for this variant (Variation ID: 409065). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. |