Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000582026 | SCV000686841 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-05 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with threonine at codon 527 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with APC-related disorders 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. |
| Labcorp Genetics |
RCV004562556 | SCV000824240 | uncertain significance | Familial adenomatous polyposis 1 | 2023-06-30 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APC protein function. ClinVar contains an entry for this variant (Variation ID: 490215). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 527 of the APC protein (p.Arg527Thr). |
| Mendelics | RCV003492109 | SCV000838076 | likely benign | Hereditary cancer | 2024-01-23 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002298697 | SCV002598567 | uncertain significance | not specified | 2022-09-30 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000582026 | SCV002710107 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-16 | criteria provided, single submitter | clinical testing | The p.R527T variant (also known as c.1580G>C), located in coding exon 12 of the APC gene, results from a G to C substitution at nucleotide position 1580. The arginine at codon 527 is replaced by threonine, an amino acid with similar properties. This alteration was detected in a cohort of 1663 Brazilian breast cancer patients who underwent hereditary multigene panel testing (Guindalini RSC et al. Sci Rep, 2022 Mar;12:4190). This amino acid position is highly conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV004562556 | SCV005053915 | uncertain significance | Familial adenomatous polyposis 1 | 2024-02-06 | criteria provided, single submitter | clinical testing |