NM_144997.7(FLCN):c.1579C>T (p.Arg527Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 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:: RCV001012272.5

Allele description [Variation Report for NM_144997.7(FLCN):c.1579C>T (p.Arg527Ter)]

NM_144997.7(FLCN):c.1579C>T (p.Arg527Ter)

Gene:

FLCN:folliculin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p11.2

Genomic location:

Preferred name:

NM_144997.7(FLCN):c.1579C>T (p.Arg527Ter)

HGVS:

NC_000017.11:g.17213816G>A
NG_008001.2:g.28373C>T
NM_001353229.2:c.1633C>T
NM_001353230.2:c.1579C>T
NM_001353231.2:c.1579C>T
NM_144997.7:c.1579C>TMANE SELECT
NP_001340158.1:p.Arg545Ter
NP_001340159.1:p.Arg527Ter
NP_001340160.1:p.Arg527Ter
NP_659434.2:p.Arg527Ter
LRG_325t1:c.1579C>T
LRG_325:g.28373C>T
NC_000017.10:g.17117130G>A
NM_144997.5:c.1579C>T
p.[Arg527*]

Protein change:

R527*

Links:

dbSNP: rs879255683

NCBI 1000 Genomes Browser:

rs879255683

Molecular consequence:

NM_001353229.2:c.1633C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001353230.2:c.1579C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001353231.2:c.1579C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_144997.7:c.1579C>T - nonsense - [Sequence Ontology: SO:0001587]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001172704	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jul 6, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 15852235, 19802896 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001172704

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jul 6, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Germline BHD-mutation spectrum and phenotype analysis of a large cohort of families with Birt-Hogg-Dubé syndrome.

Schmidt LS, Nickerson ML, Warren MB, Glenn GM, Toro JR, Merino MJ, Turner ML, Choyke PL, Sharma N, Peterson J, Morrison P, Maher ER, Walther MM, Zbar B, Linehan WM.

Am J Hum Genet. 2005 Jun;76(6):1023-33. Epub 2005 Apr 25.

PubMed [citation]

PMID:: 15852235
PMCID:: PMC1196440

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

Details of each submission

From Ambry Genetics, SCV001172704.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The p.R527* pathogenic mutation (also known as c.1579C>T), located in coding exon 11 of the FLCN gene, results from a C to T substitution at nucleotide position 1579. This changes the amino acid from an arginine to a stop codon within coding exon 11. This stop codon occurs at the 3' terminus of FLCN, is not expected to trigger nonsense-mediated mRNA decay, and removes only the last 53 amino acids of the protein. This alteration as well as several other alterations predicted to result in C-terminal truncation have been detected in multiple individuals who meet clinical diagnostic criteria for Birt-Hogg-Dube Syndrome (Schmidt LS et al. Am. J. Hum. Genet. 2005 Jun;76:1023-33; Lim DH et al. Hum. Mutat. 2010 Jan;31(1):E1043-51; Ambry internal data). Based on the majority of available evidence to date, this alteration is interpreted as a disease-causing mutation.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 16, 2025

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