Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001025682 | SCV001187922 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-08-15 | criteria provided, single submitter | clinical testing | The p.R2272S variant (also known as c.6816A>T), located in coding exon 15 of the APC gene, results from an A to T substitution at nucleotide position 6816. The arginine at codon 2272 is replaced by serine, 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. |
Invitae | RCV003769609 | SCV002240028 | uncertain significance | Familial adenomatous polyposis 1 | 2023-05-01 | 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: 826639). 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 arginine, which is basic and polar, with serine, which is neutral and polar, at codon 2272 of the APC protein (p.Arg2272Ser). |