Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001319590 | SCV001510338 | uncertain significance | Birt-Hogg-Dube syndrome | 2023-04-07 | 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) performed at Invitae indicates that this missense variant is not expected to disrupt FLCN protein function. ClinVar contains an entry for this variant (Variation ID: 1020067). This variant has not been reported in the literature in individuals affected with FLCN-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 414 of the FLCN protein (p.Arg414Trp). |
Ambry Genetics | RCV002384409 | SCV002668423 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-07-24 | criteria provided, single submitter | clinical testing | The p.R414W variant (also known as c.1240C>T), located in coding exon 8 of the FLCN gene, results from a C to T substitution at nucleotide position 1240. The arginine at codon 414 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. 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. |