ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.1522_1524del (p.Lys508del) (rs398124529)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000082629 SCV000114671 pathogenic not provided 2013-07-11 criteria provided, single submitter clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000239713 SCV000298087 likely pathogenic Multiple fibrofolliculomas 2016-07-18 criteria provided, single submitter clinical testing
GeneDx RCV000082629 SCV000321670 pathogenic not provided 2019-12-23 criteria provided, single submitter clinical testing In-frame deletion of 1 amino acid in a non-repeat region; Published functional studies demonstrate a damaging effect: impaired folliculin stability (Nahorski 2011); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at a significant frequency in large population cohorts (Lek 2016); This variant is associated with the following publications: (PMID: 19659657, 27220747, 30873309, 23364595, 30632664, 27229674, 21538689)
Invitae RCV000239713 SCV000937134 pathogenic Multiple fibrofolliculomas 2020-10-09 criteria provided, single submitter clinical testing This variant, c.1522_1524delAAG, results in the deletion of 1 amino acid of the FLCN protein (p.Lys508del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with Birt-Hogg-Dubé syndrome in one family (PMID: 19659657). It has also been observed in unrelated individuals with Birt-Hogg-Dubé syndrome (PMID: 23364595, Invitae). ClinVar contains an entry for this variant (Variation ID: 96477). Experimental studies have shown that this deletion of 1 amino acid results in an unstable FLCN protein (PMID: 21538689). For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000082629 SCV001502227 pathogenic not provided 2020-09-01 criteria provided, single submitter clinical testing

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