Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001019544 | SCV001180916 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-30 | criteria provided, single submitter | clinical testing | The p.G32E variant (also known as c.95G>A), located in coding exon 1 of the FLCN gene, results from a G to A substitution at nucleotide position 95. The glycine at codon 32 is replaced by glutamic acid, an amino acid with similar properties. This variant was identified in a cohort of 681 ancestrally diverse, healthy subjects (Bodian DL et al. PLoS One, 2014 Apr;9:e94554). This amino acid position is highly 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 | RCV001062369 | SCV001227164 | uncertain significance | Birt-Hogg-Dube syndrome | 2023-07-07 | criteria provided, single submitter | clinical testing | 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: 134424). This variant has not been reported in the literature in individuals affected with FLCN-related conditions. This variant is present in population databases (rs587778366, gnomAD 0.003%). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 32 of the FLCN protein (p.Gly32Glu). 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. |
ITMI | RCV000121100 | SCV000085268 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |