Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001052116 | SCV001216310 | uncertain significance | Birt-Hogg-Dube syndrome | 2022-03-08 | 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: 848374). This variant has not been reported in the literature in individuals affected with FLCN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 342 of the FLCN protein (p.Lys342Glu). |
| Ambry Genetics | RCV003283909 | SCV004004242 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-28 | criteria provided, single submitter | clinical testing | The p.K342E variant (also known as c.1024A>G), located in coding exon 6 of the FLCN gene, results from an A to G substitution at nucleotide position 1024. The lysine at codon 342 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is conserved. 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. |