ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.1219del (p.Ser407fs) (rs878855213)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000228856 SCV000291427 pathogenic Multiple fibrofolliculomas 2019-04-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser407Alafs*61) 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-Dub (BHD) syndrome (PMID: 27642565). ClinVar contains an entry for this variant (Variation ID: 241915). Loss-of-function variants in FLCN are known to be pathogenic (PMID: 15852235). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000255255 SCV000321663 pathogenic not provided 2016-12-07 criteria provided, single submitter clinical testing The c.1219delA variant in the FLCN gene has been reported in at least one individual with multiple spontaneous pneumothoraces and bilateral lung cysts (Burkett et al., 2016). This deletion causes a frameshift starting with codon Serine 407, changing this amino acid to an Alanine residue, and creates a premature Stop codon at position 61 of the new reading frame, denoted p.Ser407AlafsX61. This variant is predicted to result in nonsense-mediated mRNA decay or in premature protein truncation. Therefore, based on the available data, we consider c.1219delA to be pathogenic, and its presence is consistent with a risk to develop features of Birt-Hogg-Dube syndrome in this individual.

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