Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000548276 | SCV000647795 | uncertain significance | Familial adenomatous polyposis 1 | 2017-01-13 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an APC-related disease. This sequence change replaces glycine with alanine at codon 323 of the APC protein (p.Gly323Ala). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and alanine. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV000565604 | SCV000676360 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-01-20 | criteria provided, single submitter | clinical testing | The p.G323A variant (also known as c.968G>C), located in coding exon 9 of the APC gene, results from a G to C substitution at nucleotide position 968. The glycine at codon 323 is replaced by alanine, an amino acid with 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. |
Division of Medical Genetics, |
RCV000548276 | SCV001434272 | uncertain significance | Familial adenomatous polyposis 1 | 2019-10-29 | criteria provided, single submitter | clinical testing | To our knowledge, this sequence variant has not been previously reported in the literature. This variant has an overall allele frequency of 0.0001, and an allele frequency of 0.00004 in African ancestry populations, in the Broad Institute gnomAD Browser (https://gnomad.broadinstitute.org/). This allele frequency is likely too high for this variant to be associated with the classic form of FAP. In silico analyses indicate that this variant does not alter protein structure/function. Thus, it is unknown at this time whether this variant increases cancer risk. BP4; BS1 |