ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.1389C>A (p.Tyr463Ter)

dbSNP: rs137852929
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Total submissions: 5
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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 RCV000239639 SCV000298082 pathogenic Birt-Hogg-Dube syndrome 2016-07-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV000492426 SCV000580731 pathogenic Hereditary cancer-predisposing syndrome 2021-10-06 criteria provided, single submitter clinical testing The p.Y463* pathogenic mutation (also known as c.1389C>A), located in coding exon 9 of the FLCN gene, results from a C to A substitution at nucleotide position 1389. This changes the amino acid from a tyrosine to a stop codon within coding exon 9. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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 RCV000239639 SCV001433767 pathogenic Birt-Hogg-Dube syndrome 2023-08-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr463*) 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). This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 253250). This variant has not been reported in the literature in individuals affected with FLCN-related conditions.
MGZ Medical Genetics Center RCV000239639 SCV002581132 likely pathogenic Birt-Hogg-Dube syndrome 2022-08-04 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000239639 SCV004185953 pathogenic Birt-Hogg-Dube syndrome 2023-10-09 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.

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