ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.1318_1334dup (p.Leu449fs) (rs879255677)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000239636 SCV000298079 pathogenic Multiple fibrofolliculomas 2016-07-18 criteria provided, single submitter clinical testing
GeneDx RCV000483674 SCV000565010 pathogenic not provided 2018-10-18 criteria provided, single submitter clinical testing The c.1318_1334dup17 variant in the FLCN gene has not been reported previously as a pathogenicvariant, nor as a benign variant, to our knowledge. This variant causes a frameshift starting with codonLeucine 449, changes this amino acid to a Glutamine residue and creates a premature Stop codon atposition 25 of the new reading frame, denoted p.Leu449GlnfsX25. The c.1318_1334dup17 variant ispredicted to cause loss of normal protein function either through protein truncation or nonsensemediatedmRNA decay. Based on currently available evidence, we consider c.1318_1334dup17 to bepathogenic, and its presence consistent with a diagnosis of Birt-Hogg-Dube syndrome.
Ambry Genetics RCV000492447 SCV000580743 pathogenic Hereditary cancer-predisposing syndrome 2016-02-05 criteria provided, single submitter clinical testing The c.1318_1334dup17 pathogenic mutation, located in coding exon 9 of the FLCN gene, results from a duplication of GAGGTCCACGCAGCCGC at nucleotide position 1318, causing a translational frameshift with a predicted alternate stop codon. This mutation (designated as c.1833_1849dup17bp) has been reported in a familial renal cell carcinoma (RCC) kindred; however no other features of BHDS were noted by authors (Woodward ER et al.Clin.Cancer Res.2008 Sep; 14(18):5925-30).In addition to the clinical data presented in the literature, since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007.Genet Med.2008;10:294).<br /> .
Invitae RCV000239636 SCV000947110 pathogenic Multiple fibrofolliculomas 2020-03-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu449Glnfs*25) in the FLCN gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with renal cell carcinoma (PMID: 18794106,19802896). This variant is also known as c.1833_1849dup17 in the literature. ClinVar contains an entry for this variant (Variation ID: 253249). 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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