Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003537270 | SCV000957595 | uncertain significance | Familial adenomatous polyposis 1 | 2018-09-18 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with APC-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with serine at codon 2762 of the APC protein (p.Phe2762Ser). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and serine. |
| Ambry Genetics | RCV002427023 | SCV002679185 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-04-02 | criteria provided, single submitter | clinical testing | The p.F2762S variant (also known as c.8285T>C), located in coding exon 15 of the APC gene, results from a T to C substitution at nucleotide position 8285. The phenylalanine at codon 2762 is replaced by serine, an amino acid with highly dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6501 samples (13002 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.005% (greater than 21000 alleles tested) in our clinical cohort. This amino acid position is highly 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 p.F2762S remains unclear. |