Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001061632 | SCV001226381 | uncertain significance | Birt-Hogg-Dube syndrome | 2024-01-12 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 74 of the FLCN protein (p.Pro74Leu). This variant is present in population databases (rs773648142, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with FLCN-related conditions. ClinVar contains an entry for this variant (Variation ID: 856221). 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. |
Ambry Genetics | RCV002429693 | SCV002728859 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-02 | criteria provided, single submitter | clinical testing | The p.P74L variant (also known as c.221C>T), located in coding exon 1 of the FLCN gene, results from a C to T substitution at nucleotide position 221. The proline at codon 74 is replaced by leucine, an amino acid with similar properties. This amino acid position is 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. |
Fulgent Genetics, |
RCV002482059 | SCV002793089 | uncertain significance | Birt-Hogg-Dube syndrome; Familial spontaneous pneumothorax; Potocki-Lupski syndrome; Nonpapillary renal cell carcinoma; Colorectal cancer | 2022-05-18 | criteria provided, single submitter | clinical testing |