Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000204027 | SCV000261211 | uncertain significance | Familial adenomatous polyposis 1 | 2023-07-18 | 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: 220569). This missense change has been observed in individual(s) with colorectal adenomas (PMID: 14999774). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1010 of the APC protein (p.Ser1010Asn). |
| Mendelics | RCV000204027 | SCV000838098 | uncertain significance | Familial adenomatous polyposis 1 | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001018168 | SCV001179364 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-18 | criteria provided, single submitter | clinical testing | The p.S1010N variant (also known as c.3029G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 3029. The serine at codon 1010 is replaced by asparagine, an amino acid with highly similar properties. This alteration was reported in a 61-year-old individual with eight adenomas (Gismondi V et al. Int. J. Cancer 2004 May;109(5):680-4). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Color Diagnostics, |
RCV001018168 | SCV001736037 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-09 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with asparagine at codon 1010 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 colorectal adenomas (PMID: 14999774). 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 | RCV000204027 | SCV004200831 | uncertain significance | Familial adenomatous polyposis 1 | 2023-08-01 | criteria provided, single submitter | clinical testing |