Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000542554 | SCV000632824 | uncertain significance | Birt-Hogg-Dube syndrome | 2024-01-22 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 378 of the FLCN protein (p.Ser378Asn). This variant is present in population databases (rs769489773, gnomAD 0.02%). 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: 460581). 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 | RCV000568232 | SCV000673452 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-20 | criteria provided, single submitter | clinical testing | The p.S378N variant (also known as c.1133G>A), located in coding exon 7 of the FLCN gene, results from a G to A substitution at nucleotide position 1133. The serine at codon 378 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is not well 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. |
| Gene |
RCV002293449 | SCV002586550 | uncertain significance | not provided | 2023-04-07 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 17028174) |
| Laboratory of Molecular Epidemiology of Birth Defects, |
RCV003153696 | SCV003843284 | benign | Ovarian cancer | 2022-01-01 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000542554 | SCV004195322 | uncertain significance | Birt-Hogg-Dube syndrome | 2023-08-31 | criteria provided, single submitter | clinical testing |