Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003650790 | SCV001399798 | uncertain significance | Familial adenomatous polyposis 1 | 2019-10-15 | criteria provided, single submitter | clinical testing | 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with APC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with glutamic acid at codon 1749 of the APC protein (p.Gln1749Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. |
Gene |
RCV001751441 | SCV002005420 | uncertain significance | not provided | 2019-05-13 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Baylor Genetics | RCV002562623 | SCV004205338 | uncertain significance | Familial adenomatous polyposis 1 | 2023-06-15 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV003584863 | SCV004363126 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-16 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamine with glutamic acid at codon 1749 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |