Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003744661 | SCV000952929 | uncertain significance | Familial adenomatous polyposis 1 | 2023-01-20 | 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: 656241). 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 histidine, which is basic and polar, with arginine, which is basic and polar, at codon 1349 of the APC protein (p.His1349Arg). |
| Ambry Genetics | RCV003166316 | SCV003855121 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-17 | criteria provided, single submitter | clinical testing | The p.H1349R variant (also known as c.4046A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 4046. The histidine at codon 1349 is replaced by arginine, 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. |