Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV000755823 | SCV000883410 | likely benign | not provided | 2018-05-14 | criteria provided, single submitter | clinical testing | The APC c.5839A>C; p.Thr1947Pro variant, to our knowledge, is not reported in the medical literature or gene specific databases. This variant is also absent from the general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The threonine at codon 1947 is moderately conserved, but computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Additionally, the vast majority of pathogenic APC variants are truncating nonsense or frameshift variants (see InSiGHt, Kerr 2013), rather than missense variants. Based on available information, this variant is considered to be likely benign. REFERENCES Link to InSiGHt: https://www.insight-group.org/syndromes/adenomatous-polyposis/. Kerr SE et al. APC germline mutations in individuals being evaluated for familial adenomatous polyposis: a review of the Mayo Clinic experience with 1591 consecutive tests. J Mol Diagn. 2013 Jan;15(1):31-43. |
Ambry Genetics | RCV002352261 | SCV002647747 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-17 | criteria provided, single submitter | clinical testing | The p.T1947P variant (also known as c.5839A>C), located in coding exon 15 of the APC gene, results from an A to C substitution at nucleotide position 5839. The threonine at codon 1947 is replaced by proline, 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. |