Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000561596 | SCV000672554 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-16 | criteria provided, single submitter | clinical testing | The p.S1044L variant (also known as c.3131C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 3131. The serine at codon 1044 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is highly 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. |
| Color Diagnostics, |
RCV000561596 | SCV000681578 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-01-16 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with leucine at codon 1044 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed 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. |
| Invitae | RCV003652036 | SCV000820840 | uncertain significance | Familial adenomatous polyposis 1 | 2023-12-16 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1044 of the APC protein (p.Ser1044Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 485119). 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 with a negative predictive value of 95%. 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. |
| Gene |
RCV003441956 | SCV004170852 | uncertain significance | not provided | 2023-05-30 | 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; This variant is associated with the following publications: (PMID: 18199528) |
| Baylor Genetics | RCV002526901 | SCV004203301 | uncertain significance | Familial adenomatous polyposis 1 | 2023-07-26 | criteria provided, single submitter | clinical testing |