Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001011748 | SCV001172106 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-10 | criteria provided, single submitter | clinical testing | The p.H492Q variant (also known as c.1476C>A), located in coding exon 11 of the APC gene, results from a C to A substitution at nucleotide position 1476. The histidine at codon 492 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly 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 | RCV003649184 | SCV001390230 | uncertain significance | Familial adenomatous polyposis 1 | 2019-07-05 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with glutamine at codon 492 of the APC protein (p.His492Gln). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and glutamine. This variant is not present in population databases (ExAC no frequency). 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with APC-related conditions. |