ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.1547A>G (p.Lys516Arg)

dbSNP: rs2046824022
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001349162 SCV001543491 uncertain significance Birt-Hogg-Dube syndrome 2024-01-19 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 516 of the FLCN protein (p.Lys516Arg). This variant is not present in population databases (gnomAD no frequency). 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: 1044847). 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.
GeneDx RCV001751684 SCV002005712 uncertain significance not provided 2022-12-08 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; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 17028174)
Ambry Genetics RCV002404827 SCV002709328 uncertain significance Hereditary cancer-predisposing syndrome 2021-03-22 criteria provided, single submitter clinical testing The p.K516R variant (also known as c.1547A>G), located in coding exon 11 of the FLCN gene, results from an A to G substitution at nucleotide position 1547. The lysine at codon 516 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002504554 SCV002815098 uncertain significance Birt-Hogg-Dube syndrome; Familial spontaneous pneumothorax; Potocki-Lupski syndrome; Nonpapillary renal cell carcinoma; Colorectal cancer 2022-05-04 criteria provided, single submitter clinical testing
Baylor Genetics RCV001349162 SCV004195320 uncertain significance Birt-Hogg-Dube syndrome 2023-09-05 criteria provided, single submitter clinical testing

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