Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000532463 | SCV000632872 | uncertain significance | Birt-Hogg-Dube syndrome | 2024-01-05 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 151 of the FLCN protein (p.Val151Met). This variant is present in population databases (rs147164515, gnomAD 0.004%). 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: 460616). 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 expected to disrupt FLCN protein function with a positive 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. |
| Ce |
RCV000658774 | SCV000780569 | uncertain significance | not provided | 2017-11-01 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV000765334 | SCV000896597 | uncertain significance | Birt-Hogg-Dube syndrome; Familial spontaneous pneumothorax; Potocki-Lupski syndrome; Carcinoma of colon; Nonpapillary renal cell carcinoma | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001022629 | SCV001184387 | likely benign | Hereditary cancer-predisposing syndrome | 2023-06-22 | 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. |
| St. |
RCV000532463 | SCV002584577 | uncertain significance | Birt-Hogg-Dube syndrome | 2022-08-25 | criteria provided, single submitter | clinical testing | The FLCN c.451G>A (p.Val151Met) missense change has a maximum subpopulation frequency of 0.0027% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL predicts a deleterious effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with Birt-Hogg-Dubé syndrome. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |
| Baylor Genetics | RCV000532463 | SCV004195344 | uncertain significance | Birt-Hogg-Dube syndrome | 2023-07-01 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000658774 | SCV005327414 | uncertain significance | not provided | 2024-03-11 | 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 |