Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001016583 | SCV001177549 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-06 | criteria provided, single submitter | clinical testing | The p.L93F variant (also known as c.277C>T), located in coding exon 3 of the APC gene, results from a C to T substitution at nucleotide position 277. The leucine at codon 93 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is not well 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 this alteration remains unclear. |
| Invitae | RCV002550818 | SCV001232292 | uncertain significance | Familial adenomatous polyposis 1 | 2021-03-26 | 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 tolerated, 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 conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with phenylalanine at codon 93 of the APC protein (p.Leu93Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. |