Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002044332 | SCV002112372 | uncertain significance | Birt-Hogg-Dube syndrome | 2024-05-08 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 27 of the FLCN protein (p.Ala27Thr). This variant is present in population databases (rs779449668, 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: 1348461). 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 | RCV002422890 | SCV002678621 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-24 | criteria provided, single submitter | clinical testing | The p.A27T variant (also known as c.79G>A), located in coding exon 1 of the FLCN gene, results from a G to A substitution at nucleotide position 79. The alanine at codon 27 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well 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. |