ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.779+1G>T (rs758175953)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000218992 SCV000275068 pathogenic Hereditary cancer-predisposing syndrome 2017-10-27 criteria provided, single submitter clinical testing Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity;Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000239675 SCV000298060 pathogenic Multiple fibrofolliculomas 2016-07-18 criteria provided, single submitter clinical testing
GeneDx RCV000255322 SCV000321657 pathogenic not provided 2018-05-10 criteria provided, single submitter clinical testing This variant is denoted FLCN c.779+1G>T or IVS7+1G>T and consists of a G>T nucleotide substitution at the +1 position of intron 7 of the FLCN gene. This variant destroys a canonical splice donor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This variant has been reported in association with Birt-Hogg-Dub? syndrome (Toro 2008) and is considered pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000506237 SCV000603727 pathogenic not specified 2017-01-13 criteria provided, single submitter clinical testing
Invitae RCV000239675 SCV000632890 pathogenic Multiple fibrofolliculomas 2019-12-23 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 7 of the FLCN gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs758175953, ExAC 0.006%). This variant has been reported in the individuals affected with Birt Hogg Dub syndrome (PMID: 18234728, 21937013, 23050938). This variant is also known as IVS7+1 G>T in the literature. ClinVar contains an entry for this variant (Variation ID: 231274). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FLCN are known to be pathogenic (PMID: 15852235). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000762981 SCV000893426 likely pathogenic Multiple fibrofolliculomas; Pneumothorax, primary spontaneous; Potocki-Lupski syndrome; Carcinoma of colon; Renal cell carcinoma, nonpapillary 2018-10-31 criteria provided, single submitter clinical testing

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