ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.875T>G (p.Leu292Ter) (rs879255668)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000239679 SCV000298063 pathogenic Multiple fibrofolliculomas 2016-07-18 criteria provided, single submitter clinical testing
GeneDx RCV000255684 SCV000321658 pathogenic not provided 2018-11-07 criteria provided, single submitter clinical testing This variant is denoted FLCN c.875T>G at the cDNA level and p.Leu292Ter (L292X) at the protein level. The substitution creates a nonsense variant, which changes a Leucine to a premature stop codon (TTA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered pathogenic.
Ambry Genetics RCV000492726 SCV000580721 pathogenic Hereditary cancer-predisposing syndrome 2020-05-08 criteria provided, single submitter clinical testing The p.L292* pathogenic mutation (also known as c.875T>G), located in coding exon 6 of the FLCN gene, results from a T to G substitution at nucleotide position 875. This changes the amino acid from a leucine to a stop codon within coding exon 6. 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.
Invitae RCV000239679 SCV000632899 pathogenic Multiple fibrofolliculomas 2019-04-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu292*) 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 not been reported in the literature in individuals with FLCN-related conditions. ClinVar contains an entry for this variant (Variation ID: 253240). 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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