Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001932601 | SCV002136370 | uncertain significance | Birt-Hogg-Dube syndrome | 2021-07-28 | 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. 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). This sequence change replaces serine with threonine at codon 406 of the FLCN protein (p.Ser406Thr). The serine residue is highly conserved and there is a small physicochemical difference between serine and threonine. |
Ambry Genetics | RCV002359315 | SCV002655817 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-24 | criteria provided, single submitter | clinical testing | The p.S406T variant (also known as c.1217G>C), located in coding exon 8 of the FLCN gene, results from a G to C substitution at nucleotide position 1217. The serine at codon 406 is replaced by threonine, an amino acid with similar 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. |