Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000569928 | SCV000667546 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-20 | criteria provided, single submitter | clinical testing | The p.S1756F variant (also known as c.5267C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 5267. The serine at codon 1756 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This alteration was also detected on a 25-gene panel test in a Caucasian woman who was diagnosed with breast cancer before age 50 (Tung N et al. Cancer, 2015 Jan;121:25-33). This amino acid position is not 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. |
Color Diagnostics, |
RCV000569928 | SCV001344202 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-01-09 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002232115 | SCV001516231 | uncertain significance | Familial adenomatous polyposis 1 | 2023-07-12 | 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: 482341). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is present in population databases (rs773178712, gnomAD 0.006%). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 1756 of the APC protein (p.Ser1756Phe). |
Gene |
RCV001555805 | SCV001777275 | uncertain significance | not provided | 2019-12-20 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this 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: 23873622) |
Sema4, |
RCV000569928 | SCV002535142 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-16 | criteria provided, single submitter | curation | |
Baylor Genetics | RCV003465214 | SCV004207228 | uncertain significance | Familial adenomatous polyposis 1 | 2023-01-26 | criteria provided, single submitter | clinical testing | |
3DMed Clinical Laboratory Inc | RCV000677790 | SCV000803946 | uncertain significance | Carcinoma of colon | 2018-05-18 | no assertion criteria provided | clinical testing |