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:
current
Accession:
RCV000166580.4

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

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

Gene:
FLCN:folliculin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p11.2
Genomic location:
Preferred name:
NM_144997.7(FLCN):c.1389C>G (p.Tyr463Ter)
HGVS:
  • 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
Links:
OMIM: 607273.0005; dbSNP: rs137852929
NCBI 1000 Genomes Browser:
rs137852929
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]
Observations:
1

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000217382Ambry Geneticscriteria provided, single submitter
Pathogenic
(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

Description

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.

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

Last Updated: Nov 27, 2021

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