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NM_144997.7(FLCN):c.1525GAG[1] (p.Glu510del) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 6, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002392752.3

Allele description [Variation Report for NM_144997.7(FLCN):c.1525GAG[1] (p.Glu510del)]

NM_144997.7(FLCN):c.1525GAG[1] (p.Glu510del)

Gene:
FLCN:folliculin [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
17p11.2
Genomic location:
Preferred name:
NM_144997.7(FLCN):c.1525GAG[1] (p.Glu510del)
HGVS:
  • NC_000017.11:g.17214995CCT[1]
  • NG_008001.2:g.27191GAG[1]
  • NM_001353229.2:c.1579GAG[1]
  • NM_001353230.2:c.1525GAG[1]
  • NM_001353231.2:c.1525GAG[1]
  • NM_144997.7:c.1525GAG[1]MANE SELECT
  • NP_001340158.1:p.Glu528del
  • NP_001340159.1:p.Glu510del
  • NP_001340160.1:p.Glu510del
  • NP_659434.2:p.Glu510del
  • LRG_325t1:c.1528_1530del
  • LRG_325:g.27191GAG[1]
  • NC_000017.10:g.17118309CCT[1]
  • NM_144997.5:c.1528_1530delGAG
  • p.[Glu510del]
Protein change:
E510del
Links:
dbSNP: rs879255681
NCBI 1000 Genomes Browser:
rs879255681
Molecular consequence:
  • NM_001353229.2:c.1579GAG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001353230.2:c.1525GAG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001353231.2:c.1525GAG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_144997.7:c.1525GAG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Hereditary neoplastic syndrome; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002705174Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jun 6, 2023) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

BHD mutations, clinical and molecular genetic investigations of Birt-Hogg-Dubé syndrome: a new series of 50 families and a review of published reports.

Toro JR, Wei MH, Glenn GM, Weinreich M, Toure O, Vocke C, Turner M, Choyke P, Merino MJ, Pinto PA, Steinberg SM, Schmidt LS, Linehan WM.

J Med Genet. 2008 Jun;45(6):321-31. doi: 10.1136/jmg.2007.054304. Epub 2008 Jan 30. Review.

PubMed [citation]
PMID:
18234728
PMCID:
PMC2564862

A new locus-specific database (LSDB) for mutations in the folliculin (FLCN) gene.

Lim DH, Rehal PK, Nahorski MS, Macdonald F, Claessens T, Van Geel M, Gijezen L, Gille JJ, Giraud S, Richard S, van Steensel M, Menko FH, Maher ER.

Hum Mutat. 2010 Jan;31(1):E1043-51. doi: 10.1002/humu.21130.

PubMed [citation]
PMID:
19802896
See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV002705174.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

The c.1528_1530delGAG pathogenic mutation (also known as p.E510del) is located in coding exon 10 of the FLCN gene. This variant results from an in-frame GAG deletion at nucleotide positions 1528 to 1530. This results in the in-frame deletion of a glutamic acid at codon 510. This alteration has been reported in multiple individuals with personal and/or family history consistent with Birt-Hogg-Dube syndrome (Ambry internal data; Toro JR et al. J. Med. Genet., 2008 Jun;45:321-31; Benusiglio PR et al. Orphanet J Rare Dis, 2014 Oct;9:163; Furuya M et al. Cancer Sci., 2015 Mar;106:315-23; Furuya M et al. Lab. Invest., 2017 Mar;97:343-35). Further, functional analyses of this alteration have shown reduced protein expression and stability (Nahorski MS et al. Hum. Mutat., 2011 Aug;32:921-9). This alteration has demonstrated formation of perinuclear protein aggregates in another functional study (Clausen L et al. PLoS Genet, 2020 Nov;16:e1009187). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). The deleted amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 16, 2025