Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000222633 | SCV000271225 | likely pathogenic | Birt-Hogg-Dube syndrome | 2017-02-06 | criteria provided, single submitter | clinical testing | The p.Ser185Pro variant in FLCN has been reported in 1 individual with Birt Hogg Dube syndrome (BHDS), segregated with disease in 2 affected relatives (Mota-Bur gos 2013, LMM unpublished data), and was absent from large population studies. F LCN is the only gene known to be associated with BHDS and a disease causing vari ant is present in ~90% of patients. Other supporting evidence includes a strong evolutionary conservation of the affected amino acid, suggesting that a change w ould not be tolerated. In summary, although additional studies are required to f ully establish its clinical significance, the p.Ser185Pro variant is likely path ogenic. |
| Invitae | RCV000222633 | SCV003441677 | uncertain significance | Birt-Hogg-Dube syndrome | 2022-04-30 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 228263). This missense change has been observed in individuals with Birt-Hogg-Dube´ syndrome (PMID: 23414156; Invitae). This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 185 of the FLCN protein (p.Ser185Pro). This variant is not present in population databases (gnomAD no frequency). |