Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001018264 | SCV001179478 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-07 | criteria provided, single submitter | clinical testing | The p.D291E variant (also known as c.873T>G), located in coding exon 6 of the FLCN gene, results from a T to G substitution at nucleotide position 873. The aspartic acid at codon 291 is replaced by glutamic acid, an amino acid with highly similar properties. 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 this alteration remains unclear. |
| Labcorp Genetics |
RCV001342685 | SCV001536630 | uncertain significance | Birt-Hogg-Dube syndrome | 2021-08-20 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with glutamic acid at codon 291 of the FLCN protein (p.Asp291Glu). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with FLCN-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |