ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.1305del (p.Phe435fs) (rs398124527)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000082627 SCV000114669 pathogenic not provided 2013-01-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV000492221 SCV000580719 pathogenic Hereditary cancer-predisposing syndrome 2017-11-21 criteria provided, single submitter clinical testing <span style="font-size:12px"><span style="font-family:arial,helvetica,sans-serif">The c.1305delT pathogenic mutation, located in coding exon 9 of the FLCN gene, results from a deletion of one nucleotide at nucleotide position 1305, causing a translational frameshift with a predicted alternate stop codon (p.P435Lfs*33). This mutation has been described in a patient with Birt&ndash;Hogg&ndash;Dube syndrome (BHD) who had a personal history of fibrofolliculoma, renal tumor, lung cyst, and pneumothorax, and no family history of BHD (Schmidt LS et al. Am. J. Hum. Genet. 2005 Jun; 76(6):1023-33). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Invitae RCV000703847 SCV000832771 pathogenic Multiple fibrofolliculomas 2019-03-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Phe435Leufs*33) 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 observed in an individual affected with Birt-Hogg-Dubé syndrome (PMID: 15852235). This variant is also known as c.1758delT in the literature. ClinVar contains an entry for this variant (Variation ID: 96475). 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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