Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000472205 | SCV000553175 | uncertain significance | Congenital contractural arachnodactyly | 2016-08-03 | criteria provided, single submitter | clinical testing | 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. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a FBN2-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: "Benign"; Align-GVGD: "Class C25"). This sequence change replaces isoleucine with threonine at codon 1974 of the FBN2 protein (p.Ile1974Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. |