Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001227112 | SCV001399453 | uncertain significance | Birt-Hogg-Dube syndrome | 2019-08-31 | 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with alanine at codon 112 of the FLCN protein (p.Pro112Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. This variant has not been reported in the literature in individuals with FLCN-related conditions. 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: "Probably Damaging"; Align-GVGD: "Class C0"). |
| Ambry Genetics | RCV002322098 | SCV002605746 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-01 | criteria provided, single submitter | clinical testing | The p.P112A variant (also known as c.334C>G), located in coding exon 2 of the FLCN gene, results from a C to G substitution at nucleotide position 334. The proline at codon 112 is replaced by alanine, an amino acid with highly 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. |