Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002554544 | SCV001233511 | uncertain significance | Familial adenomatous polyposis 1 | 2022-12-30 | 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: 861805). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is present in population databases (rs753781948, gnomAD 0.007%). This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1970 of the APC protein (p.Ser1970Ile). |
| Ambry Genetics | RCV002355094 | SCV002652590 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-22 | criteria provided, single submitter | clinical testing | The p.S1970I variant (also known as c.5909G>T), located in coding exon 15 of the APC gene, results from a G to T substitution at nucleotide position 5909. The serine at codon 1970 is replaced by isoleucine, 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. |