Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003650535 | SCV000282803 | uncertain significance | Familial adenomatous polyposis 1 | 2023-06-15 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 2259 of the APC protein (p.Lys2259Glu). 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: 236634). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is present in population databases (rs763707129, gnomAD 0.002%). |
Gene |
RCV000482077 | SCV000568047 | uncertain significance | not provided | 2023-08-07 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Color Diagnostics, |
RCV000582672 | SCV000687093 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-30 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with glutamic acid at codon 2259 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 been identified in 1/251008 chromosomes 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. |
Counsyl | RCV000225815 | SCV000784743 | uncertain significance | Familial adenomatous polyposis 1 | 2017-11-13 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000582672 | SCV002662420 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-02-18 | criteria provided, single submitter | clinical testing | The p.K2259E variant (also known as c.6775A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 6775. The lysine at codon 2259 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Myriad Genetics, |
RCV000225815 | SCV004019767 | uncertain significance | Familial adenomatous polyposis 1 | 2023-02-15 | criteria provided, single submitter | clinical testing | This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. |