Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001011700 | SCV001172053 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-11-15 | criteria provided, single submitter | clinical testing | The p.A488T variant (also known as c.1462G>A), located in coding exon 10 of the FLCN gene, results from a G to A substitution at nucleotide position 1462. The alanine at codon 488 is replaced by threonine, an amino acid with similar properties. This amino acid position is 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. |
| Labcorp Genetics |
RCV001860680 | SCV002309789 | uncertain significance | Birt-Hogg-Dube syndrome | 2023-08-19 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 819282). 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. 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 alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 488 of the FLCN protein (p.Ala488Thr). |