Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003742712 | SCV000647519 | uncertain significance | Familial adenomatous polyposis 1 | 2021-06-17 | criteria provided, single submitter | clinical testing | In summary, this variant has uncertain impact on APC function. The available evidence is currently insufficient to determine its role 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 (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 and their clinical significance is uncertain. This variant is the result of two separate single-nucleotide changes that are in cis based on read data (c.4479A>G, ExAC 65%  and c.4480G>A, ExAC absent). This variant has not been reported in the literature in individuals with a APC-related disease. This sequence change replaces glutamine with lysine at codon 1494 of the APC protein (p.Glu1494Lys). The glutamine residue is highly conserved and there is a small  physicochemical difference between glutamine and lysine. |