Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001043407 | SCV001207151 | uncertain significance | Adams-Oliver syndrome 5 | 2021-02-25 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C55"). This variant has not been reported in the literature in individuals with NOTCH1-related conditions. This sequence change replaces threonine with alanine at codon 633 of the NOTCH1 protein (p.Thr633Ala). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and alanine. |