Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001023122 | SCV001184949 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-01-21 | criteria provided, single submitter | clinical testing | The p.S161N variant (also known as c.482G>A), located in coding exon 3 of the FLCN gene, results from a G to A substitution at nucleotide position 482. The serine at codon 161 is replaced by asparagine, 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 tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001873365 | SCV002153770 | uncertain significance | Birt-Hogg-Dube syndrome | 2023-09-27 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs760556162, gnomAD 0.003%). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 161 of the FLCN protein (p.Ser161Asn). 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: 825214). 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. 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. |