ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.1474_1475delinsG (p.Asn492fs) (rs1597578868)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001011736 SCV001172093 likely pathogenic Hereditary cancer-predisposing syndrome 2019-09-23 criteria provided, single submitter clinical testing The c.1474_1475delAAinsG variant, located in coding exon 10 of the FLCN gene, results from the deletion of two nucleotides and insertion of one nucleotide causing a translational frameshift with a predicted alternate stop codon (p.N492Afs*21). Premature stop codons are typically deleterious in nature, however, this stop codon occurs at the 3' terminus of FLCN, is not expected to trigger nonsense-mediated mRNA decay, and removes only the last 68 amino acids of the protein. The exact functional impact of these removed amino acids is unknown at this time; however, alterations predicted to result in 3' terminus truncation have been detected in individuals who meet clinical diagnostic criteria for Birt-Hogg-Dubé Syndrome (Schmidt LS et al. Am. J. Hum. Genet. 2005 Jun;76:1023-33; Lim DH et al. Hum. Mutat. 2010 Jan;31(1):E1043-51; Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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