NM_144997.7(FLCN):c.1389C>G (p.Tyr463Ter) AND Hereditary cancer-predisposing syndrome

Clinical significance:Pathogenic (Last evaluated: Sep 22, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_144997.7(FLCN):c.1389C>G (p.Tyr463Ter)]

NM_144997.7(FLCN):c.1389C>G (p.Tyr463Ter)

FLCN:folliculin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_144997.7(FLCN):c.1389C>G (p.Tyr463Ter)
  • NC_000017.11:g.17215228G>C
  • NG_008001.2:g.26961C>G
  • NM_001353229.2:c.1443C>G
  • NM_001353230.2:c.1389C>G
  • NM_001353231.2:c.1389C>G
  • NM_144997.7:c.1389C>GMANE SELECT
  • NP_001340158.1:p.Tyr481Ter
  • NP_001340159.1:p.Tyr463Ter
  • NP_001340160.1:p.Tyr463Ter
  • NP_659434.2:p.Tyr463Ter
  • LRG_325t1:c.1389C>G
  • LRG_325:g.26961C>G
  • LRG_325p1:p.Tyr463Ter
  • NC_000017.10:g.17118542G>C
  • NM_144997.5:c.1389C>G
  • p.Y463*
  • p.[Tyr463*]
Protein change:
Y463*; TYR463TER
OMIM: 607273.0005; dbSNP: rs137852929
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001353229.2:c.1443C>G - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001353230.2:c.1389C>G - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001353231.2:c.1389C>G - nonsense - [Sequence Ontology: SO:0001587]
  • NM_144997.7:c.1389C>G - nonsense - [Sequence Ontology: SO:0001587]


Hereditary cancer-predisposing syndrome
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
MONDO: MONDO:0015356; MedGen: C0027672

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000217382Ambry Geneticscriteria provided, single submitter
(Sep 22, 2020)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Details of each submission

From Ambry Genetics, SCV000217382.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided


The p.Y463* pathogenic mutation (also known as c.1389C>G), located in coding exon 9 of the FLCN gene, results from a C to G substitution at nucleotide position 1389. This changes the amino acid from a tyrosine to a stop codon within coding exon 9. This mutation has been observed in multiple individuals with Birt-Hogg-Dubé syndrome (Schmidt LS et al. Am. J. Hum. Genet. 2005 Jun;76(6):1023-33; Toro JR et al. J. Med. Genet. 2008 Jun;45(6):321-31), including one large family where the mutation co-segregated with disease in six of six affected individuals (Nickerson ML et al. Cancer Cell. 2002 Aug;2(2):157-64). 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.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Nov 27, 2021

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