Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003534721 | SCV000833146 | uncertain significance | Familial adenomatous polyposis 1 | 2023-03-18 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 580616). 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. 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 glutamine, which is neutral and polar, at codon 2116 of the APC protein (p.His2116Gln). |
| Color Diagnostics, |
RCV001183571 | SCV001349362 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-09-25 | criteria provided, single submitter | clinical testing | This missense variant replaces histidine with glutamine at codon 2116 of the APC protein. Computational prediction tool is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV001183571 | SCV002657959 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-02 | criteria provided, single submitter | clinical testing | The p.H2116Q variant (also known as c.6348T>G), located in coding exon 15 of the APC gene, results from a T to G substitution at nucleotide position 6348. The histidine at codon 2116 is replaced by glutamine, 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. |