ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.235_238del (p.Ser79fs) (rs750146811)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000222354 SCV000278166 pathogenic Hereditary cancer-predisposing syndrome 2019-02-19 criteria provided, single submitter clinical testing Strong segregation with disease (lod >3 = >10 meioses);Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000239626 SCV000298039 pathogenic Multiple fibrofolliculomas 2016-07-18 criteria provided, single submitter clinical testing
GeneDx RCV000255605 SCV000321649 pathogenic not provided 2018-05-01 criteria provided, single submitter clinical testing This deletion of four nucleotides in FLCN is denoted c.235_238delTCGG at the cDNA level and p.Ser79ThrfsX50 (S79TfsX50) at the protein level. The normal sequence, with the bases that are deleted in brackets, is AAAG[delTCGG]ACAT. The deletion causes a frameshift which changes a Serine to a Threonine at codon 79, and creates a premature stop codon at position 50 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.235_238delTCGG has been reported in a large Finnish kindred with familial primary spontaneous pneumothorax (Painter 2005). We consider this variant to be pathogenic.
Invitae RCV000239626 SCV001387569 pathogenic Multiple fibrofolliculomas 2019-06-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser79Thrfs*50) in the FLCN gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed to segregate with bullous lung lesions and pneumothorax in a family (PMID: 15657874). ClinVar contains an entry for this variant (Variation ID: 3371). Loss-of-function variants in FLCN are known to be pathogenic (PMID: 15852235). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000003538 SCV000023696 pathogenic Pneumothorax, primary spontaneous 2009-09-01 no assertion criteria provided literature only

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