ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.158del (p.Gln53fs) (rs1131690825)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492196 SCV000580722 pathogenic Hereditary cancer-predisposing syndrome 2020-05-22 criteria provided, single submitter clinical testing The c.158delA pathogenic mutation, located in coding exon 1 of the FLCN gene, results from a deletion of one nucleotide at nucleotide position 158, causing a translational frameshift with a predicted alternate stop codon (p.Q53Rfs*2). This mutation has been reported in multiple individuals with Birt-Hogg-Dube syndrome (Whitworth J et al. Fam. Cancer, 2017 01;16:139-142; Rossing M et al. J. Hum. Genet., 2017 Feb;62:151-157). 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.
GeneDx RCV000520861 SCV000616722 pathogenic not provided 2017-09-05 criteria provided, single submitter clinical testing This deletion of one nucleotide in FLCN is denoted c.158delA at the cDNA level and p.Gln53ArgfsX2 (Q53RfsX2) at the protein level. The normal sequence, with the base that is deleted in brackets, is ATTC[delA]GATG. The deletion causes a frameshift which changes a Glutamine to an Arginine at codon 53, and creates a premature stop codon at position 2 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. FLCN c.158delA has been reported in association with Birt-Hogg-Dub? syndrome (Rossing 2016, Whitworth 2016). We consider this variant to be pathogenic.
Invitae RCV001390962 SCV001592871 pathogenic Multiple fibrofolliculomas 2020-02-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln53Argfs*2) 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 individual(s) with Birt-Hogg-Dubé syndrome (PMID: 27722904, 27734835). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 428637). 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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