Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003651978 | SCV000647696 | uncertain significance | Familial adenomatous polyposis 1 | 2023-03-24 | 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: 470080). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 2389 of the APC protein (p.Ser2389Asn). |
| Ambry Genetics | RCV000564175 | SCV000667356 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-28 | criteria provided, single submitter | clinical testing | The p.S2389N variant (also known as c.7166G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 7166. The serine at codon 2389 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is well 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000586700 | SCV000694109 | uncertain significance | not provided | 2017-07-03 | criteria provided, single submitter | clinical testing | Variant summary: The c.7166G>A (p.Ser2389Asn) in APC gene is a missense variant involves a mildly conserved nucleotide and 3/5 in silico tools predict deleterious outcome. The variant is located within the basic domain, however no functional studies supporting deleterious outcome of this alteration on the protein function have been published at the time of evaluation. The variant is absent from the control population dataset of ExAC, but is present at a low frequency in gnomAD (0.000004081; 1/245052 chrs tested), which does not exceed the maximal expected allele frequency for a disease causing allele in APC gene (0.00007). To our knowledge, the variant has not been reported in affected individuals via published reports nor has it been cited by reputable databases/clinical laboratories. Taken together, the variant was classified as VUS, until new information becomes available. |
| Fulgent Genetics, |
RCV000765790 | SCV000897179 | uncertain significance | Desmoid disease, hereditary; Carcinoma of colon; Familial adenomatous polyposis 1; Neoplasm of stomach; Hepatocellular carcinoma | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000564175 | SCV000905274 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-08 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with asparagine at codon 2389 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 APC-related disorders in the literature. This variant has been identified in 1/250312 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000586700 | SCV002046430 | uncertain significance | not provided | 2020-11-17 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV002527861 | SCV004191417 | uncertain significance | Familial adenomatous polyposis 1 | 2023-09-08 | criteria provided, single submitter | clinical testing |