Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001055965 | SCV001220380 | uncertain significance | Birt-Hogg-Dube syndrome | 2022-04-25 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 851547). This variant has not been reported in the literature in individuals affected with FLCN-related conditions. This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 59 of the FLCN protein (p.Arg59Pro). This variant is not present in population databases (gnomAD no frequency). |
| Ambry Genetics | RCV002400318 | SCV002714735 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-21 | criteria provided, single submitter | clinical testing | The p.R59P variant (also known as c.176G>C), located in coding exon 1 of the FLCN gene, results from a G to C substitution at nucleotide position 176. The arginine at codon 59 is replaced by proline, an amino acid with dissimilar properties. This amino acid position is conserved. 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. |