Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000213600 | SCV000278298 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-15 | criteria provided, single submitter | clinical testing | The p.S1415C variant (also known as c.4243A>T), located in coding exon 15 of the APC gene, results from an A to T substitution at nucleotide position 4243. The serine at codon 1415 is replaced by cysteine, an amino acid with dissimilar 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. |
| Invitae | RCV003743678 | SCV000647504 | uncertain significance | Familial adenomatous polyposis 1 | 2023-03-20 | 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on APC protein function. ClinVar contains an entry for this variant (Variation ID: 233841). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1415 of the APC protein (p.Ser1415Cys). |
| Color Diagnostics, |
RCV000213600 | SCV002053571 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-17 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with cysteine at codon 1415 of the APC protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 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. |
| Sema4, |
RCV000213600 | SCV002531993 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-17 | criteria provided, single submitter | curation | |
| Baylor Genetics | RCV002516164 | SCV004203279 | uncertain significance | Familial adenomatous polyposis 1 | 2023-07-27 | criteria provided, single submitter | clinical testing |