Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000570961 | SCV000673423 | benign | Hereditary cancer-predisposing syndrome | 2022-08-03 | criteria provided, single submitter | clinical testing | This alteration is classified as 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. |
| Invitae | RCV000635566 | SCV000756983 | uncertain significance | Birt-Hogg-Dube syndrome | 2024-01-06 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 546 of the FLCN protein (p.Asn546Ser). This variant is present in population databases (rs775149348, gnomAD 0.006%). 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: 485586). 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. |
| Center for Genomic Medicine, |
RCV002268200 | SCV002551236 | uncertain significance | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV002461370 | SCV002757356 | uncertain significance | not provided | 2022-05-24 | 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: 17028174) |
| Fulgent Genetics, |
RCV002483537 | SCV002794403 | uncertain significance | Birt-Hogg-Dube syndrome; Familial spontaneous pneumothorax; Potocki-Lupski syndrome; Nonpapillary renal cell carcinoma; Colorectal cancer | 2022-04-12 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000635566 | SCV004195340 | uncertain significance | Birt-Hogg-Dube syndrome | 2023-07-14 | criteria provided, single submitter | clinical testing |