Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000702195 | SCV000831039 | uncertain significance | Birt-Hogg-Dube syndrome | 2023-12-23 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 533 of the FLCN protein (p.Gln533His). This variant is present in population databases (rs190965235, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with FLCN-related conditions. ClinVar contains an entry for this variant (Variation ID: 579021). 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 with a negative predictive value of 80%. 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. |
Ambry Genetics | RCV002397458 | SCV002707823 | likely benign | Hereditary cancer-predisposing syndrome | 2022-07-12 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Gene |
RCV003236837 | SCV003935811 | uncertain significance | not provided | 2023-11-07 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 23675308, 17028174) |
Prevention |
RCV003420249 | SCV004115459 | uncertain significance | FLCN-related condition | 2022-11-24 | criteria provided, single submitter | clinical testing | The FLCN c.1599G>C variant is predicted to result in the amino acid substitution p.Gln533His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.010% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-17117110-C-G). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Center for Genomic Medicine, |
RCV003493713 | SCV004242770 | uncertain significance | not specified | 2024-02-06 | criteria provided, single submitter | clinical testing |