Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001193494 | SCV001362374 | uncertain significance | not specified | 2019-01-14 | criteria provided, single submitter | clinical testing | Variant summary: APC c.1321C>G (p.Pro441Ala) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 245278 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1321C>G in individuals affected with Familial Adenomatous Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Invitae | RCV003538600 | SCV001378633 | uncertain significance | Familial adenomatous polyposis 1 | 2020-12-17 | criteria provided, single submitter | clinical testing | 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with alanine at codon 441 of the APC protein (p.Pro441Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. |
Ambry Genetics | RCV002379749 | SCV002694863 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-12 | criteria provided, single submitter | clinical testing | The p.P441A variant (also known as c.1321C>G), located in coding exon 10 of the APC gene, results from a C to G substitution at nucleotide position 1321. The proline at codon 441 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |