Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000474054 | SCV000549471 | uncertain significance | Birt-Hogg-Dube syndrome | 2023-01-06 | 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 409404). This variant has not been reported in the literature in individuals affected with FLCN-related conditions. This variant is present in population databases (rs751478971, gnomAD 0.0009%). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 326 of the FLCN protein (p.Pro326Ser). |
| Ambry Genetics | RCV002379460 | SCV002695139 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-13 | criteria provided, single submitter | clinical testing | The p.P326S variant (also known as c.976C>T), located in coding exon 6 of the FLCN gene, results from a C to T substitution at nucleotide position 976. The proline at codon 326 is replaced by serine, an amino acid with similar properties. This amino acid position is not well 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. |