Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000773673 | SCV000907372 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-02-09 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000825284 | SCV000966576 | uncertain significance | not specified | 2018-08-10 | criteria provided, single submitter | clinical testing | The p.Gly1921Cys variant in APC has not been previously reported in individuals with adenomatous polyposis and was absent from large population studies. Computa tional prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary the clinical significance of the p.Gly1921Cys variant is uncertain. ACMG/AMP Criteria applied: PM2. |
Ambry Genetics | RCV000773673 | SCV001186524 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-15 | criteria provided, single submitter | clinical testing | The p.G1921C variant (also known as c.5761G>T), located in coding exon 15 of the APC gene, results from a G to T substitution at nucleotide position 5761. The glycine at codon 1921 is replaced by cysteine, an amino acid with highly dissimilar properties. 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. |
Gene |
RCV001759453 | SCV002005439 | uncertain significance | not provided | 2019-04-15 | criteria provided, single submitter | clinical testing | Not observed [at a significant frequency] in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge |
Invitae | RCV003768346 | SCV002252033 | uncertain significance | Familial adenomatous polyposis 1 | 2023-06-19 | 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: 628990). 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 glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 1921 of the APC protein (p.Gly1921Cys). |