Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003535973 | SCV000947536 | uncertain significance | Familial adenomatous polyposis 1 | 2022-03-22 | 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 2496 of the APC protein (p.His2496Arg). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 652009). 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 | RCV001026485 | SCV001188878 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-14 | criteria provided, single submitter | clinical testing | The p.H2496R variant (also known as c.7487A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 7487. The histidine at codon 2496 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. |