Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV004564071 | SCV000552553 | uncertain significance | Familial adenomatous polyposis 1 | 2016-06-24 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with phenylalanine at codon 643 of the APC protein (p.Ser643Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a APC-related disease. 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. 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. |
| Ambry Genetics | RCV001013737 | SCV001174360 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-08-21 | criteria provided, single submitter | clinical testing | The p.S643F variant (also known as c.1928C>T), located in coding exon 14 of the APC gene, results from a C to T substitution at nucleotide position 1928. The serine at codon 643 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |