Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000222438 | SCV000274508 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-15 | criteria provided, single submitter | clinical testing | The p.T256S variant (also known as c.766A>T), located in coding exon 4 of the FLCN gene, results from an A to T substitution at nucleotide position 766. The threonine at codon 256 is replaced by serine, an amino acid with similar properties. This amino acid position is 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. |
| Invitae | RCV000808271 | SCV000948371 | uncertain significance | Birt-Hogg-Dube syndrome | 2020-01-09 | 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with FLCN-related disease. ClinVar contains an entry for this variant (Variation ID: 230834). This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with serine at codon 256 of the FLCN protein (p.Thr256Ser). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and serine. |