Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004524837 | SCV005030731 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-02-25 | criteria provided, single submitter | clinical testing | The p.G235D variant (also known as c.704G>A), located in coding exon 4 of the FLCN gene, results from a G to A substitution at nucleotide position 704. The glycine at codon 235 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV005100654 | SCV005738726 | uncertain significance | Birt-Hogg-Dube syndrome | 2024-04-29 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 235 of the FLCN protein (p.Gly235Asp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FLCN-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FLCN protein function with a negative predictive value of 80%. 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. |