Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001812438 | SCV001471942 | uncertain significance | not provided | 2020-05-05 | criteria provided, single submitter | clinical testing | The FLCN c.1697T>C; p.Met566Thr variant (rs756302545), to our knowledge, is not reported in the medical literature or gene-specific databases. This variant is found on a single chromosome (1/31402 alleles) in the Genome Aggregation Database. The methionine at codon 566 is highly conserved, but computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Met566Thr variant is uncertain at this time. |
| Ambry Genetics | RCV002402810 | SCV002714234 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-26 | criteria provided, single submitter | clinical testing | The p.M566T variant (also known as c.1697T>C), located in coding exon 11 of the FLCN gene, results from a T to C substitution at nucleotide position 1697. The methionine at codon 566 is replaced by threonine, 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 deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV002541771 | SCV003490015 | uncertain significance | Birt-Hogg-Dube syndrome | 2024-04-16 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 566 of the FLCN protein (p.Met566Thr). This variant is present in population databases (rs756302545, gnomAD 0.007%). 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: 993694). 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. |
| Baylor Genetics | RCV004570668 | SCV005058683 | uncertain significance | Birt-Hogg-Dube syndrome 1 | 2024-02-08 | criteria provided, single submitter | clinical testing |