Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000165394 | SCV000216121 | pathogenic | Hereditary cancer-predisposing syndrome | 2017-02-27 | criteria provided, single submitter | clinical testing | The p.Y405* pathogenic mutation (also known as c.1215C>G), located in coding exon 8 of the FLCN gene, results from a C to G substitution at nucleotide position 1215. This changes the amino acid from a tyrosine to a stop codon within coding exon 8. This pathogenic mutation has been described in individuals with clinical features of Birt-Hogg-Dubé syndrome (Toro JR et al. J. Med. Genet. 2008 Jun;45:321-31; Park HJ et al. PLoS ONE 2017 Feb;12:e0170713). Of note, this alteration is also designated as c.1670C>G in published literature. In addition to the clinical data presented in the literature, 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 | RCV001219608 | SCV001391556 | pathogenic | Birt-Hogg-Dube syndrome | 2023-08-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr405*) in the FLCN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FLCN are known to be pathogenic (PMID: 15852235). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 185892). This premature translational stop signal has been observed in individual(s) with clinical diagnosis or suspicion of Birt-Hogg-Dubé syndrome (PMID: 18234728, 28151982). This variant is not present in population databases (gnomAD no frequency). |
Myriad Genetics, |
RCV001219608 | SCV004188963 | pathogenic | Birt-Hogg-Dube syndrome | 2023-09-21 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |