Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000804774 | SCV000944699 | uncertain significance | Birt-Hogg-Dube syndrome | 2023-08-17 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FLCN protein function. ClinVar contains an entry for this variant (Variation ID: 649767). 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 0.02%). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 21 of the FLCN protein (p.Cys21Tyr). |
| Ambry Genetics | RCV001025105 | SCV001187232 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-03-02 | criteria provided, single submitter | clinical testing | The p.C21Y variant (also known as c.62G>A), located in coding exon 1 of the FLCN gene, results from a G to A substitution at nucleotide position 62. The cysteine at codon 21 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Gene |
RCV001766672 | SCV002008287 | uncertain significance | not provided | 2019-09-19 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |