Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001217150 | SCV001388983 | uncertain significance | Birt-Hogg-Dube syndrome | 2024-08-14 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 271 of the FLCN protein (p.Glu271Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with BHD syndrome (PMID: 33057194). ClinVar contains an entry for this variant (Variation ID: 946308). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt FLCN protein function with a positive 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 | RCV002418747 | SCV002678260 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-14 | criteria provided, single submitter | clinical testing | The p.E271K variant (also known as c.811G>A), located in coding exon 5 of the FLCN gene, results from a G to A substitution at nucleotide position 811. The glutamic acid at codon 271 is replaced by lysine, an amino acid with similar 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. |
Baylor Genetics | RCV001217150 | SCV004199792 | uncertain significance | Birt-Hogg-Dube syndrome | 2023-09-21 | criteria provided, single submitter | clinical testing |