ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.890_893del (p.Glu297fs) (rs398124541)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000082644 SCV000114686 pathogenic not provided 2013-04-03 criteria provided, single submitter clinical testing
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000239720 SCV000298064 pathogenic Multiple fibrofolliculomas 2016-07-18 criteria provided, single submitter clinical testing
GeneDx RCV000082644 SCV000565006 pathogenic not provided 2015-07-24 criteria provided, single submitter clinical testing The c.890_893delAAAG variant in the FLCN gene has been reported previously inassociation with familial renal cell carcinoma (Woodward et al., 2008) using alternatenomenclature and has been seen previously in patients at GeneDx referred for FLCN geneanalysis. The deletion causes a frameshift starting with codon Glutamic Acid 297, changesthis amino acid to an Alanine residue and creates a premature Stop codon at position 25 ofthe new reading frame, denoted p.Glu297AlafsX25. This variant is predicted to cause lossof normal protein function either through protein truncation or nonsense-mediated mRNAdecay. Therefore, we interpret the c.890_893delAAAG variant as pathogenic.
Ambry Genetics RCV000492401 SCV000580734 pathogenic Hereditary cancer-predisposing syndrome 2019-10-29 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV000239720 SCV000836092 pathogenic Multiple fibrofolliculomas 2019-06-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu297Alafs*25) in the FLCN gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs398124541, ExAC 0.001%). This variant has been observed to segregate with Birt-Hogg-Dub_x0001_e (BHD) syndrome in several families (PMID: 27643397, 27470329, 19785621). Additionally, this variant has been reported in an individual affected with isolated renal cell cancer, who later presented with pulmonary features (PMID: 18794106), and an individual affected with colorectal cancer (PMID: 27356891). This variant is also known as c.1388_1391delAAAG in the literature. ClinVar contains an entry for this variant (Variation ID: 96492). Loss-of-function variants in FLCN are known to be pathogenic (PMID: 15852235). For these reasons, this variant has been classified as Pathogenic.

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