Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000805647 | SCV000945611 | uncertain significance | Birt-Hogg-Dube syndrome | 2025-01-19 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 64 of the FLCN protein (p.Ala64Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 650488). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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. |
| Revvity Omics, |
RCV003144627 | SCV003832711 | uncertain significance | not provided | 2022-02-04 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003166248 | SCV003882225 | likely benign | Hereditary cancer-predisposing syndrome | 2022-11-03 | 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. |
| Myriad Genetics, |
RCV004789206 | SCV005406343 | likely benign | Birt-Hogg-Dube syndrome 1 | 2024-08-09 | criteria provided, single submitter | clinical testing | This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. |
| Fulgent Genetics, |
RCV005012334 | SCV005643857 | uncertain significance | Familial spontaneous pneumothorax; Nonpapillary renal cell carcinoma; Colorectal cancer; Birt-Hogg-Dube syndrome 1 | 2024-03-08 | criteria provided, single submitter | clinical testing |