Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001025056 | SCV001187178 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-24 | criteria provided, single submitter | clinical testing | The p.H2090R variant (also known as c.6269A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 6269. The histidine at codon 2090 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is well 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. |
| Invitae | RCV003537420 | SCV001205643 | uncertain significance | Familial adenomatous polyposis 1 | 2023-10-22 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 2090 of the APC protein (p.His2090Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 826279). 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. 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. |
| Color Diagnostics, |
RCV001025056 | SCV001341679 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-01-31 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001776085 | SCV002012967 | uncertain significance | not provided | 2020-09-08 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |