Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000082622 | SCV000114664 | uncertain significance | not provided | 2014-02-14 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000472239 | SCV000549439 | uncertain significance | Birt-Hogg-Dube syndrome | 2024-01-28 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 400 of the FLCN protein (p.Val400Phe). This variant is not present in population databases (gnomAD no frequency). 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: 96472). 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 | RCV001010250 | SCV001170417 | likely benign | Hereditary cancer-predisposing syndrome | 2022-06-07 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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. |
| Sema4, |
RCV001010250 | SCV002530101 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-28 | criteria provided, single submitter | curation | |
| Gene |
RCV000082622 | SCV002762510 | uncertain significance | not provided | 2022-12-06 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); 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: 17028174) |
| Baylor Genetics | RCV000472239 | SCV004199796 | uncertain significance | Birt-Hogg-Dube syndrome | 2023-09-19 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000082622 | SCV004218913 | uncertain significance | not provided | 2023-05-24 | criteria provided, single submitter | clinical testing | To the best of our knowledge, this variant has not been reported in the published literature. The frequency of this variant in the general population, 0.0000066 (1/152120 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |