Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001059031 | SCV001223635 | uncertain significance | Birt-Hogg-Dube syndrome | 2021-09-25 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with serine at codon 290 of the FLCN protein (p.Ala290Ser). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and serine. 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. This variant has not been reported in the literature in individuals affected with FLCN-related conditions. This variant is not present in population databases (ExAC no frequency). |
Ambry Genetics | RCV002374943 | SCV002684121 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-01 | criteria provided, single submitter | clinical testing | The p.A290S variant (also known as c.868G>T), located in coding exon 5 of the FLCN gene, results from a G to T substitution at nucleotide position 868. The alanine at codon 290 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. |