Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001206003 | SCV001377289 | 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) performed at Invitae indicates that this missense variant is expected to disrupt FLCN protein function. ClinVar contains an entry for this variant (Variation ID: 937061). This variant has not been reported in the literature in individuals affected with FLCN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 247 of the FLCN protein (p.Asp247Gly). |
| Ambry Genetics | RCV002379780 | SCV002673098 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-21 | criteria provided, single submitter | clinical testing | The p.D247G variant (also known as c.740A>G), located in coding exon 4 of the FLCN gene, results from an A to G substitution at nucleotide position 740. The aspartic acid at codon 247 is replaced by glycine, an amino acid with similar properties. This amino acid position is well 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. |