ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.584del (p.Gly195fs) (rs878855217)

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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 RCV000492527 SCV000580726 pathogenic Hereditary cancer-predisposing syndrome 2016-08-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense),Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000230881 SCV000298050 pathogenic Multiple fibrofolliculomas 2016-07-18 criteria provided, single submitter clinical testing
GeneDx RCV000255719 SCV000321655 pathogenic not provided 2018-06-15 criteria provided, single submitter clinical testing The c.584delG variant in the FLCN gene has been previously reported in association with Birt-Hogg-Dube syndrome (Schmidt et al., 2005; Toro et al., 2008; Rossing et al., 2016). This deletion causes a frameshift starting with codon Glycine 195, changes this amino acid to a Glutamic Acid residue and creates a premature Stop codon at position 28 of the new reading frame, denoted p.Gly195GlufsX28. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Based on the currently available evidence, we consider c.584delG to be pathogenic.
GenomeConnect, ClinGen RCV000230881 SCV000607195 not provided Multiple fibrofolliculomas no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Invitae RCV000230881 SCV000291448 pathogenic Multiple fibrofolliculomas 2018-10-11 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 6 of the FLCN mRNA (c.584delG), causing a frameshift at codon 195. This creates a premature translational stop signal (p.Gly195Glufs*28) and is expected to result in an absent or disrupted protein product. Truncating variants in FLCN are known to be pathogenic. This particular truncation has been reported in multiple individuals affected with Birt-Hogg-Dubé syndrome (PMID: 15852235, 18234728). This variant is also known as c.1036delG and c.1039delG. For these reasons, this variant has been classified as Pathogenic.

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