Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000806975 | SCV000946999 | uncertain significance | Birt-Hogg-Dube syndrome | 2023-08-28 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 651581). This variant has not been reported in the literature in individuals affected with FLCN-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.004%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 42 of the FLCN protein (p.Gly42Arg). |
| Ambry Genetics | RCV001010539 | SCV001170755 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-11 | criteria provided, single submitter | clinical testing | The p.G42R variant (also known as c.124G>C), located in coding exon 1 of the FLCN gene, results from a G to C substitution at nucleotide position 124. The glycine at codon 42 is replaced by arginine, an amino acid with dissimilar 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. |