Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002389115 | SCV002701686 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-20 | criteria provided, single submitter | clinical testing | The p.F465L variant (also known as c.1395T>G), located in coding exon 9 of the FLCN gene, results from a T to G substitution at nucleotide position 1395. The phenylalanine at codon 465 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003607505 | SCV004429652 | uncertain significance | Birt-Hogg-Dube syndrome | 2023-01-09 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 1771638). This variant has not been reported in the literature in individuals affected with FLCN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 465 of the FLCN protein (p.Phe465Leu). |