Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000705955 | SCV000834981 | uncertain significance | Birt-Hogg-Dube syndrome | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 356 of the FLCN protein (p.Leu356Val). This variant is present in population databases (rs757313788, gnomAD 0.04%). 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: 581992). 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 | RCV001009833 | SCV001169947 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-27 | criteria provided, single submitter | clinical testing | The p.L356V variant (also known as c.1066C>G), located in coding exon 7 of the FLCN gene, results from a C to G substitution at nucleotide position 1066. The leucine at codon 356 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly 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. |
| Gene |
RCV002245615 | SCV002513756 | uncertain significance | not provided | 2023-01-06 | criteria provided, single submitter | clinical testing | 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) |
| Baylor Genetics | RCV000705955 | SCV004195335 | uncertain significance | Birt-Hogg-Dube syndrome | 2023-08-06 | criteria provided, single submitter | clinical testing |