Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003537087 | SCV000647734 | uncertain significance | Familial adenomatous polyposis 1 | 2023-05-02 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 2605 of the APC protein (p.Gln2605His). 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: 470111). 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). |
| Ambry Genetics | RCV001026842 | SCV001189304 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-10-07 | criteria provided, single submitter | clinical testing | The p.Q2605H variant (also known as c.7815A>C), located in coding exon 15 of the APC gene, results from an A to C substitution at nucleotide position 7815. The glutamine at codon 2605 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is 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. |