ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.221C>T (p.Pro74Leu)

gnomAD frequency: 0.00001  dbSNP: rs773648142
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001061632 SCV001226381 uncertain significance Birt-Hogg-Dube syndrome 2024-01-12 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 74 of the FLCN protein (p.Pro74Leu). This variant is present in population databases (rs773648142, gnomAD 0.0009%). 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: 856221). 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 RCV002429693 SCV002728859 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-02 criteria provided, single submitter clinical testing The p.P74L variant (also known as c.221C>T), located in coding exon 1 of the FLCN gene, results from a C to T substitution at nucleotide position 221. The proline at codon 74 is replaced by leucine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002482059 SCV002793089 uncertain significance Birt-Hogg-Dube syndrome; Familial spontaneous pneumothorax; Potocki-Lupski syndrome; Nonpapillary renal cell carcinoma; Colorectal cancer 2022-05-18 criteria provided, single submitter clinical testing

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