Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001341829 | SCV001535722 | uncertain significance | Birt-Hogg-Dube syndrome | 2023-08-17 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 1038509). 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 proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 428 of the FLCN protein (p.Pro428Thr). |
| Ambry Genetics | RCV002377450 | SCV002689468 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-09-10 | criteria provided, single submitter | clinical testing | The p.P428T variant (also known as c.1282C>A), located in coding exon 8 of the FLCN gene, results from a C to A substitution at nucleotide position 1282. The proline at codon 428 is replaced by threonine, an amino acid with highly similar properties. This amino acid position is poorly 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. |