Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001012340 | SCV001172774 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-29 | criteria provided, single submitter | clinical testing | The p.T532P variant (also known as c.1594A>C), located in coding exon 11 of the FLCN gene, results from an A to C substitution at nucleotide position 1594. The threonine at codon 532 is replaced by proline, 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 deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001860702 | SCV002186749 | uncertain significance | Birt-Hogg-Dube syndrome | 2024-03-06 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 532 of the FLCN protein (p.Thr532Pro). This variant is present in population databases (rs753023144, gnomAD 0.002%). 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: 819626). 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. |