ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.1584del (p.Glu530fs) (rs1131690827)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492254 SCV000580725 likely pathogenic Hereditary cancer-predisposing syndrome 2017-10-24 criteria provided, single submitter clinical testing The c.1584delC variant, located in coding exon 11 of the FLCN gene, results from a deletion of one nucleotide at nucleotide position 1584, causing a translational frameshift with a predicted alternate stop codon (p.E530Rfs*7). Premature stop codons are typically deleterious in nature, however, this stop codon occurs at the 3' terminus of FLCN, and is not expected to trigger nonsense-mediated mRNA decay, and removes only the last 44 amino acids of the protein. The exact functional impact of these removed amino acids is unknown at this time. However, this alteration as well as another frameshift alteration with the same predicted premature termination codon have been detected in multiple individuals who meet clinical diagnostic criteria for Birt-Hogg-Dubé Syndrome (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
GeneDx RCV000657381 SCV000779114 likely pathogenic not provided 2017-09-15 criteria provided, single submitter clinical testing This deletion of one nucleotide in FLCN is denoted c.1584delC at the cDNA level and p.Glu530ArgfsX7 (E530RfsX7) at the protein level. The normal sequence, with the base that is deleted in brackets, is GACC[delC]AAAG. The deletion causes a frameshift which changes a Glutamic Acid to an Arginine at codon 530, and creates a premature stop codon at position 7 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through protein truncation. Based on the currently available information, we consider this deletion to be a likely pathogenic variant.

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