Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000989761 | SCV001140314 | uncertain significance | Birt-Hogg-Dube syndrome | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Center for Genomic Medicine, |
RCV002268396 | SCV002551366 | uncertain significance | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002327215 | SCV002629976 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-28 | criteria provided, single submitter | clinical testing | The c.427_429delTTC variant (also known as p.F143del) is located in coding exon 3 of the FLCN gene. This variant results from an in-frame TTC deletion at nucleotide positions 427 to 429. This results in the in-frame deletion of a phenylalanine at codon 143. This variant has been reported in three siblings with primary spontaneous pneumothoraces and a family history of renal cancer; however, absence of this alteration in unaffected relatives was not confirmed (Kim J et al. Gene, 2012 May;499:339-42). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV000989761 | SCV003220909 | uncertain significance | Birt-Hogg-Dube syndrome | 2023-06-23 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs764153620, gnomAD 0.001%). This variant, c.427_429del, results in the deletion of 1 amino acid(s) of the FLCN protein (p.Phe143del), but otherwise preserves the integrity of the reading frame. Experimental studies have shown that this variant affects FLCN function (PMID: 22446046). 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. Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 803328). This variant has been observed in individual(s) with Birt–Hogg–Dubé syndrome (PMID: 22446046). It has also been observed to segregate with disease in related individuals. |