Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000463825 | SCV000549435 | uncertain significance | Birt-Hogg-Dube syndrome | 2023-04-24 | criteria provided, single submitter | clinical testing | 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FLCN protein function. ClinVar contains an entry for this variant (Variation ID: 409377). This variant has not been reported in the literature in individuals affected with FLCN-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 280 of the FLCN protein (p.Glu280Lys). |
| Ambry Genetics | RCV002436434 | SCV002677714 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-08 | criteria provided, single submitter | clinical testing | The p.E280K variant (also known as c.838G>A), located in coding exon 5 of the FLCN gene, results from a G to A substitution at nucleotide position 838. The glutamic acid at codon 280 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 tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |