Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Centre of Medical Genetics, |
RCV000655250 | SCV000747184 | uncertain significance | Adams-Oliver syndrome 5 | 2017-12-01 | criteria provided, single submitter | research | |
Invitae | RCV000655250 | SCV000777180 | uncertain significance | Adams-Oliver syndrome 5 | 2017-10-10 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with asparagine at codon 528 of the NOTCH1 protein (p.Asp528Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs757988142, ExAC 0.003%). This variant has not been reported in the literature in individuals with NOTCH1-related disease. 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: "Possibly Damaging"; Align-GVGD: "Class C15"). 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. |