Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003765280 | SCV000254019 | uncertain significance | Familial adenomatous polyposis 1 | 2024-11-04 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1663 of the APC protein (p.Glu1663Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 216168). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt APC protein function with a negative predictive value of 95%. 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. |
Ambry Genetics | RCV000568323 | SCV000667460 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-18 | criteria provided, single submitter | clinical testing | The p.E1663K variant (also known as c.4987G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 4987. The glutamic acid at codon 1663 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well 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. |
Mendelics | RCV002247624 | SCV002516886 | uncertain significance | not specified | 2022-05-04 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002478702 | SCV002777960 | uncertain significance | Desmoid disease, hereditary; Familial adenomatous polyposis 1; Hepatocellular carcinoma; Gastric cancer; Colorectal cancer; Gastric adenocarcinoma and proximal polyposis of the stomach | 2021-11-10 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000568323 | SCV004361475 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-07 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with lysine at codon 1663 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. |
Baylor Genetics | RCV003765280 | SCV005052573 | uncertain significance | Familial adenomatous polyposis 1 | 2023-11-26 | criteria provided, single submitter | clinical testing |