Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000561033 | SCV000672551 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-14 | criteria provided, single submitter | clinical testing | The p.S2799P variant (also known as c.8395T>C), located in coding exon 15 of the APC gene, results from a T to C substitution at nucleotide position 8395. The serine at codon 2799 is replaced by proline, an amino acid with similar properties. This amino acid position is 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. |
| Labcorp Genetics |
RCV004562465 | SCV000820724 | likely benign | Familial adenomatous polyposis 1 | 2025-01-02 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000561033 | SCV001734796 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-11-09 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with proline at codon 2799 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004586805 | SCV005076929 | uncertain significance | not specified | 2024-04-08 | criteria provided, single submitter | clinical testing | Variant summary: APC c.8395T>C (p.Ser2799Pro) results in a non-conservative amino acid change located in the EB-1 binding domain (IPR009232) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 238630 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.8395T>C in individuals affected with Familial Adenomatous Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 485117). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| All of Us Research Program, |
RCV004806482 | SCV005430136 | uncertain significance | Classic or attenuated familial adenomatous polyposis | 2024-05-14 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with proline at codon 2799 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. |