Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000817735 | SCV000958314 | uncertain significance | Birt-Hogg-Dube syndrome | 2023-09-08 | criteria provided, single submitter | clinical testing | 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 expected to disrupt FLCN protein function. ClinVar contains an entry for this variant (Variation ID: 134425). This variant has not been reported in the literature in individuals affected with FLCN-related conditions. This variant is present in population databases (rs587778367, gnomAD 0.002%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 168 of the FLCN protein (p.Arg168Cys). 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. |
Sema4, |
RCV002255131 | SCV002530143 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-23 | criteria provided, single submitter | curation | |
Ambry Genetics | RCV002255131 | SCV002641803 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-27 | criteria provided, single submitter | clinical testing | The p.R168C variant (also known as c.502C>T), located in coding exon 3 of the FLCN gene, results from a C to T substitution at nucleotide position 502. The arginine at codon 168 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Laboratory of Molecular Epidemiology of Birth Defects, |
RCV003153396 | SCV003843580 | likely pathogenic | Ovarian cancer | 2022-01-01 | criteria provided, single submitter | clinical testing | |
ITMI | RCV000121102 | SCV000085270 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |